BACKGROUND & AIMS: Flexible sigmoidoscopy (FS) is recommended for mass screening for colorectal cancer (CRC), yet little is known about the risk of adverse events when FS is used in general clinical practice. We aimed to determine the incidence of gastrointestinal complications and acute myocardial infarction (MI) after screening FS. METHODS: Northern California Kaiser Permanente Medical Care Program members of average risk for CRC (n = 107,704) who underwent screening FS during 1994 to 1996 (109,534 FS), as part of the Colorectal Cancer Prevention (CoCaP) program. The main outcome measure was hospitalization for gastrointestinal complications or acute MI within 4 weeks of FS. RESULTS: The mean age of subjects was 61 years, and 48.8% were female. Nongastroenterologist physicians, nurses, or physician assistants performed 72% of FS. Overall, 24 persons were hospitalized for a gastrointestinal complication. Of these, 7 were serious (2 perforations, 2 episodes of diverticulitis requiring surgery, 2 cases of bleeding requiring transfusion, and 1 episode of unexplained colitis). In multivariate models, complications were significantly more common in men than in women (odds ratio, 3.34; 95% confidence interval [CI], 1.34-10.13). MI occurred in 33 persons within 4 weeks of FS, but the incidence for this period was similar to that in the subsequent 48 weeks (rate ratio, 0.8; 95% CI, 0.6-1.2). CONCLUSIONS: The risk of serious complications after screening FS in this setting appears to be modest. Although MI occurs after FS, the risk during the 4 weeks after the procedure appears to be similar to expectations for persons of screening age.