The APC Trial was a placebo-controlled randomized study of celecoxib for prevention of sporadic adenomas in high risk patients. This study showed that, after 3 years of treatment, patients taking 200 mg of celecoxib bid had 33% fewer adenomas and 57% fewer advanced lesions, and patients taking 400 mg of celecoxib bid had 45% fewer adenomas and 66% fewer advanced lesions. This study also found that celecoxib use was associated with a small but significant increase in cardiovascular risk. After completing the 3 year treatment study, APC trial enrollees were offered participation in a 2 year off treatment observational study during which additional safety and efficacy data were collected. Colonoscopies at 5 years after initiating study treatment were performed on 639 patients, and showed a cumulative advanced adenoma incidence of 0.125 in patients taking 200 mg bid celecoxib, and 0.158 in patients taking 400 mg celecoxib bid, compared to 0.212 for patients on placebo (41% and 25% reductions, respectively, P<0.0001). Investigator reported, non-adjudicated selected cardiovascular events occurred 35 times in 676 patients randomized to placebo, 45 times in 683 patients randomized to celecoxib 200 mg bid, and 46 times in 669 patients randomized to 400 mg celecoxib bid. This selected category of events included all reports of myocardial infarction or ischemia, death from any cause, cerebrovascular disease, cardiovascular therapeutic procedures, or venous thrombosis or thromboembolism. One third of APC Trial participants used cardioprotective aspirin, and year 5 colonoscopy data showed increased adenoma incidence and severity in this subset, suggesting the presence of more aggressive disease in aspirin users. These data, together with additional new placebo-controlled analyses of celecoxib cardiovascular safety, suggest that chemoprevention with celecoxib may be safe and effective for some high risk colorectal adenoma patients.