Data regarding the outcomes of restarting anticoagulation in patients who develop gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized that restarting anticoagulation in these patients is associated with better outcomes. This is a retrospective cohort study that enrolled subjects who developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was defined by history and electrocardiography on presentation. GIB was defined as a decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic evaluation. Time-to-event adjusted analyses were performed to find an association of restarting warfarin and recurrent GIB, arterial thromboembolism, and mortality. Stratified analysis by duration of interruption of warfarin was also performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was associated with decreased thromboembolism (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.54 to 0.93, p = 0.01) and reduced mortality (HR 0.67, 95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to 1.10, p = 0.47). When the outcomes were stratified by duration of warfarin interruption, restarting warfarin after 7 days was not associated with increased risk of GIB but was associated with decreased risk of mortality and thromboembolism compared with resuming after 30 days of interruption. Decision to restart warfarin after an episode of major GIB is associated with improved survival and decreased thromboembolism without increased risk of GIB after 7 days of interruption.