To evaluate gastrointestinal and cardiovascular adverse event risks associated with optical colonoscopy (OC) among Medicare outpatients who received computed tomography colonography (CTC) as their initial method of colorectal evaluation.Medicare claims were compared between 6114 outpatients ≥66years who received initial CTC and 149,202 outpatients who received initial OC between January 2007 and December 2008. OC patients were matched on county of residence and year of evaluation. Outcomes included lower gastrointestinal bleeding, gastrointestinal perforation, other gastrointestinal events and cardiovascular events resulting in an emergency department visit or hospitalization within 30days.Among 1000 outpatients undergoing initial CTC, 12.4 experienced lower gastrointestinal bleeding, 0.7 perforation, 18.0 other gastrointestinal events and 45.5 cardiovascular events within 30days. After multivariate adjustment, risks of lower gastrointestinal bleeding, other gastrointestinal events and cardiovascular events were higher with initial OC than CTC, with or without subsequent OC (Odds Ratio 1.91 95 Confidence Interval [1.47,2.49], Odds Ratio 1.35 95 Confidence Interval [1.07,1.69] and Odds Ratio 1.38 95 Confidence Interval [1.18,1.62], respectively); however, perforation risk did not differ (p=0.10). This pattern is similar in older and symptomatic populations.Rates of gastrointestinal bleeding, other gastrointestinal events and cardiovascular events are lower following initial CTC than OC, but rates of perforation do not differ.