Bleeding is a potentially serious complication after Roux-en-Y gastric bypass (RYGB). Preventive measures and therapeutic strategies have not been adequately defined. We reviewed data on 742 consecutive patients treated at the University of California San Francisco to identify cases of early and late bleeding (less or greater than 30 days after surgery) after RYGB. Bleeding was defined as symptoms or signs of bleeding, associated with blood transfusion. We recorded patient characteristics, details of the operative technique, diagnostic approach, therapeutic strategies, and outcomes. Twenty-six patients (3.5%) had postoperative bleeding, which mostly occurred in the first 30 days postoperatively (N=19). Hematocrit decreased significantly from preoperative values (-5.2 ± 3.1 without bleeding vs. -14.8 ± 4.7 with, p<0.01). Type 2 diabetes was more prevalent in patients who had bleeding (58% vs. 32%, p=0.03). No other patient characteristics or details of the operative technique were associated with different rates of bleeding. Therapeutic intervention other than transfusion was needed for seven patients with early bleeding (36.8%) and for all patients with late bleeding. Four patients with early bleeding required reoperation. Early bleeding source was intraluminal in four patients, intraperitoneal in five, and self-limited and of unknown location in ten. Late bleeding occurred on average at 62.6 months (range, 5 to 300 months) after index surgery, five patients required reoperation, and the source was always intraluminal. Bleeding after RYGB may be from various anatomic sites; details of the operative technique were not associated with different rates of bleeding, and therapy should be tailored to suspected location of bleeding.