Introduction and Objectives: Contrasting data have been reported on bivalirudin as an anticoagulation strategy during percutaneous coronary interventions, offering theoretical benefits on bleeding complications but raising concerns on a potential increase in the risk of stent thrombosis. We performed an updated meta-analysis to evaluate the efficacy and safety of bivalirudin compared with unfractionated heparin in patients undergoing percutaneous interventions for acute coronary syndromes., Methods: Literature archives and main scientific sessions were scanned. The primary efficacy endpoint was 30-day overall mortality. Secondary endpoints were stent thrombosis and major bleeding. A prespecified analysis was conducted according to clinical presentation., Results: Twelve randomized trials were included, involving 32 746 patients (52.5% randomized to bivalirudin). Death occurred in 1.8% of the patients, with no differences between bivalirudin and heparin (odds ratio = 0.91; 95% confidence interval, 0.77-1.08; P = .28; P for heterogeneity = .41). Similar results were obtained for patients with non-ST-segment elevation and in ST-segment elevation myocardial infarction. A significantly higher rate of stent thrombosis was observed with bivalirudin (odds ratio = 1.42; 95% confidence interval, 1.09-1.83; P = .008; P for heterogeneity = .09). Bivalirudin was associated with a significant reduction in the rate of major bleeding (odds ratio = 0.60; 95% confidence interval, 0.54-0.75; P < .00001; P for heterogeneity < .0001), which, however, was related to the differential use of glycoprotein IIb/IIIa inhibitors (r = -0.02 [-0.033 to -0.0032]; P = .02) and did not translate into survival benefits., Conclusions: In patients undergoing percutaneous coronary interventions, bivalirudin is not associated with a reduction in mortality compared with heparin but does increase stent thrombosis. The reduction in bleeding complications observed with bivalirudin does not translate into survival benefits but is rather influenced by a differential use of glycoprotein IIb/IIIa inhibitors., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)