Purpose: The management of ulcers with adherent clots is controversial. We performed a meta-analysis to compare endoscopic (EndoRx) and medical therapy (MedRx) for patients with bleeding peptic ulcers containing adherent clots. Methods: We used MEDLINE, Biosis, Embase, and the Cochrane Library to identify all randomized controlled trials comparing the two interventions. The primary authors of published articles were contacted and study databases combined for a patient-level analysis. Studies in abstract form were included in a traditional meta-analysis. Outcomes evaluated were recurrent bleeding, need for surgery, length of hospitalization, transfusion requirement, and mortality. A random effects model was used to calculate the pooled relative risks (RR) and the number needed to treat (NNT). Results: Six studies were identified, representing 240 patients from the U.S., Hong Kong, South Korea, and Spain. Four studies (N = 146) were fully published and two were in abstract form. Eligibility criteria, interventions, and outcome definitions were similar. All patients received general supportive care and acid suppressive therapy. Patients in the EndoRx group also underwent endoscopic clot removal and treatment of the underlying lesion with thermal energy, electrocoagulation, and/or injection of sclerosants. The two groups were similar in demographic characteristics, severity of bleeding, risk factors for ulcer disease, and comorbidities. Rebleeding occurred in 5 of 61 (8.2%) patients in the EndoRx group, compared to 21 of 85 (24.7%) in the MedRx group (p = 0.01). The pooled RR of rebleeding was 0.35 (95% CI, 0.14–0.83; NNT = 6.3) in favor of EndoRx. There was no difference between EndoRx and MedRx in length of hospital stay (mean 6.8 versus 5.6 days, p = 0.37), transfusions (mean 3.0 versus 2.8 units of packed red blood cells, p = 0.58), and mortality (9.8% versus 7%, p = 0.55). The results of the meta-analysis were concordant with the patient-level analysis, except for the need for surgery which favored endoscopic therapy (pooled RR 0.43; 95% CI, 0.19–0.98; NNT = 13.3); however this outcome became non-significant when only peer-reviewed studies were considered. Conclusions: Endoscopic therapy is superior to medical therapy for preventing recurrent hemorrhage in patients with bleeding peptic ulcers and adherent clot. The interventions are comparable with respect to the need for surgery, length of hospital stay, transfusion requirement, and mortality.