Background & Aims: Aberrant crypt foci (ACF) are the putative precursor of colorectal adenomas. However, there are limited data available on the prevalence and risk factors for ACF. Methods: Subjects from the Prostate, Lung, Colorectal and Ovarian cancer screening trial were recruited for an ACF study, with subjects with adenoma history being oversampled. By using a standardized protocol of magnified chromoendoscopy with methylene blue staining (up to the middle rectal fold), ACF were photo-documented and removed for histologic evaluation. Results: A total of 505 (66% male; 55% ≥70 y) subjects from 4 institutions were examined; 42% had no adenoma, 32% had nonadvanced distal adenoma, and 25% had advanced distal adenoma at the baseline Prostate, Lung, Colorectal and Ovarian cancer screening trial examination (8.2 years before ACF examination on average). A total of 68% of this population had 1 or more ACF, 43% had 1 to 3, 19% had 4 to 6, and 5% had 7 or more. Baseline adenoma status was not associated with ACF prevalence (range, 66%-69%) or mean number of ACF (range, 3.1-3.5). Of 143 endoscopic ACF examined histologically, 68.5% were confirmed to be ACF. In a logistic model, current (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-5.6) and former smoking (OR, 1.6; 95% CI, 1.1-2.5) were associated with higher ACF prevalence; a body mass index greater than 30 was associated with lower prevalence (OR, 0.53; 95% CI, 0.35-0.8). Age, sex, family history of colorectal cancer, and aspirin/nonsteroidal anti-inflammatory drug use were not associated significantly with ACF prevalence. Conclusions: ACF prevalence and number were not associated with adenoma history, and only 68.5% of endoscopic ACF were confirmed histologically. These results raise concern about the use of ACF as a surrogate marker of colorectal cancer risk.