In 2010, an Oxford neurologist named Peter Rothwell published a paper in The Lancet that rewrote medical guidelines around the world. After analyzing eight randomized trials and twenty-five thousand patients, he showed that taking a daily aspirin cut your long-term risk of dying from cancer by about a third [1].
By 2016, the US Preventive Services Task Force had officially recommended a daily aspirin for the prevention of colorectal cancer [2]. Millions of people walked into their pharmacies and started taking a small white tablet every morning — not for their hearts, but to lower their cancer risk.
Then a trial from Australia delivered one of the most disturbing results in modern medicine. Nineteen thousand people. Half on aspirin, half on placebo. And the people on aspirin started dying first [3].
A note before we go further: this article is about primary prevention — taking aspirin when you've had no cardiovascular event. If your doctor has prescribed it after a heart attack, a stroke, or a stent, that's secondary prevention, a different conversation, and you should not stop based on this article. Talk to your doctor first.
Everything else from here is about the millions of people taking aspirin without that history, hoping to prevent a future they were told it could prevent.
Table of Contents
- The Consensus
- The Challenger
- The 2026 Confirmation
- The Mystery
- The Exception
- What You Should Do
- References
The Consensus
The first hint that aspirin might do something to cancer came out of Melbourne in 1988. A surgeon named Gabriel Kune was running a large case-control study comparing 715 colorectal cancer patients to 727 healthy controls. He noticed something he wasn't looking for. The cancer patients were taking aspirin less often than the healthy ones. After adjusting for diet, age, sex, and other factors, aspirin use was an independent protective effect, consistent across colon and rectal cancers and across both sexes [4].
It was a single observational study. But it kicked off a wave of research. Over the following two decades, more than a hundred observational studies pointed in the same direction — people who took aspirin appeared to get less cancer [5].
But observational data has a fundamental problem: you can't tell whether the aspirin is preventing the cancer, or whether the kind of person who takes aspirin is the kind of person who gets less cancer for other reasons. To know which it was, someone needed randomized trial evidence. And that's where Peter Rothwell came in.
Rothwell is a neurologist at Oxford. He'd spent his career running aspirin trials in stroke patients — about 20,000 of them over fifteen years. He realized that scattered across all the old cardiovascular trials, there was buried data on cancer outcomes. Data nobody had pooled together. So he did.
In 2010, he published the result. A 21% reduction in cancer deaths overall — and the benefit grew with time. After five years on aspirin, the reduction reached about a third. After 7.5 years or more, gastrointestinal cancer deaths fell by more than half [1].
Then he kept going. Two more papers in 2012, both in The Lancet. Aspirin reduced metastasis [6]. And the evidence of longer-term cancer reduction was strengthened [7].
Guidelines worldwide were rewritten. In 2016, the US Preventive Services Task Force officially recommended a daily low-dose aspirin for primary prevention in people aged 50 to 59 — partly for the heart, but specifically including colorectal cancer [2].
Rothwell received international research awards. The narrative felt settled. Aspirin — the cheapest, oldest drug in the cabinet — was a cancer shield.
The Challenger
But that satisfying story was about to take an unexpected twist.
John McNeil, a professor of epidemiology at Monash University, just down the road from where Gabriel Kune had run that original 1988 study, had been watching the aspirin-and-cancer story unfold for two decades. What he kept coming back to was this: every single trial Rothwell pooled had originally been designed to study heart attacks and strokes. Cancer wasn't the primary endpoint in any of them. The cancer outcomes had been pulled out after the fact. The participants were younger — on average, in their fifties and sixties. The doses were often higher — some trials used 300 milligrams or more. And the longest benefits Rothwell observed only emerged at 15 to 20 years of follow-up, using cancer registry data after the trials had ended.
Meanwhile, often the people actually swallowing a daily aspirin to prevent cancer weren't 50-year-olds in a heart trial. They were 70-year-olds at a pharmacy, taking 100 milligrams, hoping for a benefit they expected within a few years.
McNeil saw an enormous practice happening on shaky evidence — millions of older adults taking a drug nobody had properly tested in them. So he set out to run that trial.
He called it ASPREE — Aspirin in Reducing Events in the Elderly. Nineteen thousand, one hundred and fourteen people. All over 70, or over 65 if they were Black or Hispanic. None of them with cardiovascular disease at the start. None of them with dementia. None of them with disability. The healthiest cohort of older adults you could possibly assemble. Half got 100 milligrams of aspirin every day. Half got placebo [3].
McNeil and his team enlisted more than 2,000 GPs across Australia and the US to keep track of every participant [8]. Then they waited. Five years went by.
The data came back. McNeil opened the spreadsheet, expecting either a positive result that would vindicate Rothwell, or a null result that would mean ASPREE had been too short.
He got neither.
In 2018, the first major paper came out. Three papers, actually, all published the same day in the New England Journal of Medicine. The cardiovascular finding was that aspirin didn't prevent first heart attacks or strokes in this population [9]. Disappointing, but not shocking. Other primary prevention trials had hinted at this. The shocking finding was buried in a different paper.
People taking aspirin were dying more often. And the deaths were driven by cancer [3].
This was the exact opposite of what Rothwell's work predicted. Even McNeil himself wouldn't quite believe it. In the study's conclusion, he said the result needed to be interpreted with caution [3].
Maybe it was a fluke. Maybe five years wasn't long enough — Rothwell's benefits, after all, mostly appeared at five years and beyond. Give the trial more time, and perhaps the cancer benefit would finally emerge.
Which Preventative Strategies Actually Make Sense For You?
The aspirin story shows that one-size-fits-all health advice can age badly. Health Roadmap gives evidence-based health suggestions tailored to your age, history, and risk factors — so you can make decisions like this with current data, not 15-year-old guidelines.
Get Your Personalized Health PlanSo they kept following these 19,114 people. For another four and a half years. The results just came out.
The 2026 Confirmation
The follow-up paper landed in JAMA Oncology in early 2026. Median follow-up: 8.6 years. Three thousand four hundred and forty-eight new cancers. Eleven hundred and seventy-three cancer deaths. The numbers were too large to dismiss as a statistical fluke [10].
The lead author was Suzanne Orchard, an associate professor at Monash and the director of the ASPREE extension study. She told an interviewer that "most everyone would like to think that aspirin would be this wonder drug." The data they had just published said otherwise [11].
Cancer incidence — identical to placebo. Colorectal cancer specifically — the cancer aspirin was supposed to prevent, the entire reason the USPSTF made its 2016 recommendation — also identical to placebo. A hazard ratio of 1.01. As if the drug wasn't there at all [10].
But cancer death told a different story. Fifteen percent more cancer deaths in the aspirin group [10].
Think about what that means in human terms. ASPREE was a trial of healthy older adults. The kind of person who could plausibly live to 95 if nothing went wrong. And in this trial, healthy older adults, randomly assigned to a drug their doctors had recommended for cancer prevention, were dying of cancer 15% more often than the people who got the placebo pill.
There was one strange detail, though. When researchers looked at the four-and-a-half year period after participants stopped taking aspirin, the increased mortality vanished. There was no lasting harm. Whatever aspirin was doing, it was doing it while people were on the drug. Stop the drug, and the effect stopped with it [10].
And it wasn't just one trial anymore. A few weeks after the JAMA Oncology paper, the Cochrane Library — the gold standard of medical evidence reviews — published an updated analysis pooling 10 randomized trials and 124,837 participants [12].
In the 5-to-10 year window — the time period that applies to most older adults who started aspirin in their sixties or seventies — colorectal cancer mortality was 77% higher in the aspirin group. They rate the evidence for this finding, however, as "low certainty" [12].
The Cochrane authors did find a possible benefit at fifteen years or longer of continuous use, but they rated that "very low certainty" — the weakest evidence rating on the scale [12].
The US Preventive Services Task Force had already quietly withdrawn the colorectal cancer recommendation back in 2022, after the early ASPREE results [13].
As of today, no major guideline body recommends aspirin for cancer prevention in the general population. The decade-long consensus is gone.
But here's what really bothers me about all this. If you go back to the laboratory and look at how aspirin works against cancer, the drug should be helping. Not hurting. And just last year, researchers at Cambridge proved exactly that — in a paper that should have been the final piece of evidence for aspirin as a cancer drug.
The Mystery
The paper was published in Nature, based on the work of a team led by Professor Rahul Roychoudhuri and Dr. Jie Yang [14].
They were studying how cancer cells spread through the body — metastasis. And they found something elegant.
When a cancer cell breaks off from a tumor and tries to seed a new metastasis somewhere else in the body, it doesn't travel alone. It travels surrounded by platelets — the small cells your blood uses to form clots. Those platelets release a molecule called thromboxane A2, or TXA2. And TXA2 has a hidden role nobody had appreciated. It puts the brakes on T cells — the immune cells that hunt and kill rogue cancer cells. Effectively, the cancer cell uses platelets like a personal escort, releasing a chemical that tells the immune system to stand down [14].
"It was a Eureka moment when we found TXA2 was the molecular signal that activates this suppressive effect on T cells," Yang told reporters at the time. Aspirin, at low doses, does exactly one thing very well — it shuts down platelet production of TXA2. That's how it prevents heart attacks [14].
So in theory, low-dose aspirin should release the brakes on T cells, unleashing their anti-cancer activity. The Cambridge team showed in mouse experiments that this is exactly what happens [15].
So aspirin, mechanistically, should prevent cancer from spreading. It should reduce metastatic deaths and prolong life. In mice, that's exactly what it does.
But in 19,114 healthy older adults, in the largest randomized trial ever run on this question, it does the opposite. There were more cancer deaths. The exact reverse of what the Cambridge mechanism would predict.
How? The honest answer is that we don't fully know. But the ASPREE team themselves have proposed three serious hypotheses, and they may all be partly true.
The first is what's called immunosenescence. As we age, our T cells become less responsive to everything. Releasing the TXA2 brake doesn't help if the T cells themselves can't accelerate. The Cambridge experiments were done in young, healthy mice with vigorous immune systems. ASPREE was done in 70-year-olds. By that age, the immune machinery aspirin is supposed to unleash may simply not be there to unleash anymore [10].
The second is more troubling. Aspirin's anti-inflammatory effects might mask the early symptoms of cancer. The aches, the fatigue, the low-grade fevers, the inflammation around a growing tumor — aspirin can quietly suppress all of them. People on aspirin may not notice a cancer until it's larger and harder to treat. Cancer caught early leads to death less often. Cancer caught late is more likely to be fatal. If the aspirin in your medicine cabinet is dimming the warning lights on your dashboard, that could potentially explain the ASPREE result. Though the researchers judge this to be unlikely what's going on [16].
The third is the most uncomfortable. Inflammation isn't just a bystander in cancer. It's part of how the body identifies and isolates dangerous cells. Suppress that inflammation chronically, every day for years, and you may be giving established tumors more room to grow undisturbed. The same drug that helps a young immune system kill metastasizing cells in a Cambridge mouse may give an old, less vigilant immune system a quiet permission to lose its grip [10].
Which of these is right, no one yet knows. But there is one group of patients where aspirin's cancer-prevention benefit is unambiguous. And that group changes how we should think about the whole story.
The Exception
In 2020, a trial called CAPP2 published its 10-year follow-up results in The Lancet. The participants weren't healthy older adults. They were carriers of Lynch syndrome — a genetic condition that gives a person up to a 60% lifetime risk of colorectal cancer. The aspirin dose wasn't 100 milligrams. It was 600 milligrams a day — six times higher. The mean age wasn't 74. It was 45 — close to half the age of the average ASPREE participant [5, 17].
The results? A 35% reduction in colorectal cancer [17].
In Lynch syndrome carriers, aspirin works. It does exactly what Rothwell's data said it would do.
Which means Peter Rothwell wasn't wrong. The Oxford team found something real. Aspirin can prevent cancer — but only in the right person, at the right dose, started young enough, and continued long enough.
The mistake was in extrapolating that effect to a healthy 74-year-old taking 100 milligrams for five years. Different person. Different dose. Different time horizon. Different result. And in older adults, the mismatch isn't just "the drug doesn't help" — it's "the drug appears to harm."
Which raises a question millions of people are now asking themselves. What do you do, today, with the bottle of aspirin in your kitchen cupboard?
What You Should Do
Let me start with the warning I gave at the beginning, because it is by far the most important part of this article. If your doctor has prescribed aspirin after a heart attack, a stroke, a stent, or any cardiovascular event — keep taking it unless they tell you otherwise. That is secondary prevention. The evidence for aspirin in that setting is strong, well-replicated, and stopping it on your own can be fatal. None of what I've just said today changes that. If you're not sure whether your aspirin is for primary or secondary prevention, the answer is: ask your doctor.
What does change, based on ASPREE and the Cochrane review, is the case for taking aspirin when you have no cardiovascular history, hoping it'll prevent cancer. That case has collapsed for older adults. There is no signal of benefit. There is a signal of harm.
And there is a separate, well-established harm that I haven't even gotten to yet. A 59% increase in serious bleeding outside the brain. That's stomach bleeds, the kind of bleeding that puts people in hospital. The Cochrane review rated this one as high certainty — the strongest evidence rating on the scale. That's the cost side of the ledger that doesn't depend on the cancer story at all [12].
So here's the practical breakdown.
If you're a healthy older adult taking a daily aspirin to prevent cancer or "just in case" — talk to your doctor about whether it still makes sense. The evidence has moved.
If you have Lynch syndrome — talk to a gastroenterologist. The CAPP2 protocol works, but it's a higher dose and needs medical supervision.
And if you're younger, in your forties or fifties, with a strong family history of cancer, the picture is genuinely uncertain. The Rothwell data may still apply to you, taken over a much longer time horizon than has yet been formally tested in your age group. That's a discussion to have with your own doctor, weighing your personal bleeding risk and your family history. There isn't a clean answer.
Peter Rothwell wasn't wrong. But the context is crucial. It's a reminder that every time you hear "studies show," it's worth asking the same three questions a researcher would: which studies? In whom? And over what time frame? Sometimes the answer changes everything.
Which Preventative Strategies Actually Make Sense For You?
The aspirin story shows that one-size-fits-all health advice can age badly. Health Roadmap gives evidence-based health suggestions tailored to your age, history, and risk factors — so you can make decisions like this with current data, not 15-year-old guidelines.
Get Your Personalized Health PlanReferences
1. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62110-1/abstract
3. https://www.nejm.org/doi/10.1056/NEJMoa1803955
4. https://pubmed.ncbi.nlm.nih.gov/3390835/
5. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30366-4/fulltext
6. https://pubmed.ncbi.nlm.nih.gov/22440947/
7. https://pubmed.ncbi.nlm.nih.gov/22440946/
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC6456041/
9. https://www.nejm.org/doi/10.1056/NEJMoa1805819
10. https://jamanetwork.com/journals/jamaoncology/article-abstract/2844193
12. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015266.pub2/full
13. https://jamanetwork.com/journals/jama/fullarticle/2791399
15. https://www.nature.com/articles/s41586-025-08626-7
