Hemoclips are utilized for treating bleeding gastrointestinal angiodysplastic lesions (GIADs); however, the supporting evidence is limited. Our aim is to evaluate the efficacy of hemoclips in preventing bleeding secondary to GIADs compared to argon plasma coagulation (APC). This retrospective study included patients with bleeding gastric, small bowel or colonic GIADs that were endoscopically treated between January 2009 and November 2016. Patients that received hemoclips as monotherapy or in combination were compared to a randomly selected similar number of patients treated with APC. We included 157 patients that underwent APC and 141 who received hemoclips. During a median follow-up of 17 months, those with hemoclips had a 32.6% rebleeding vs. 46.5% in the APC group (P = 0.017). On multivariate regression analysis, use of hemoclips was not a significant predictor of rebleeding when compared to APC; hemoclips monotherapy (HR, 0.92; 95% CI, 0.54-1.59) and hemoclips combination (HR, 0.65; 95% CI, 0.41-1.01). When the multivariate analysis was restricted to subjects that resumed antithrombotics after endoscopy, rebleeding risk was lower when hemoclips were used in combination (HR, 0.46; 95% CI, 0.25-0.84) compared to APC. We noted a similar effect in the antithrombotic subgroup even after propensity score matching (HR, 0.51; 95% CI, 0.27-0.95). Treatment modality was not a significant predictor of rebleeding when studied for the entire population. However, the risk of rebleeding was lower with hemoclips combination therapy compared to APC in patients that resumed antithrombotic therapy, suggesting a potential role for a combined approach in this subgroup of patients.