Percutaneous coronary intervention (PCI) has become the most common mode of coronary revascularization. Inhibition of platelet aggregation via glycoprotein (GP) IIb/IIIa receptor blockade significantly reduces the acute ischemic complications associated with PCI, but the risk of bleeding may also be increased with these agents. The purpose of the present study was to provide an up-to-date meta-analysis on the clinical efficacy and safety of intravenous GP IIb/IIIa antagonists in patients undergoing PCI. A comprehensive search was undertaken to identify all randomized trials of GP IIb/IIIa antagonists versus control in patients intended to undergo PCI. Medline, Embase, Biosis, HealthStar and hand searches were performed. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), repeat revascularization, thrombocytopenia and bleeding. OR and their 95% CI were calculated using the random effects model. Twenty-one randomized trials were identified, which together included 23,941 patients. The mortality rate at seven days was 0.33% in the GP IIb/IIa group compared with 0.50% in the control group (OR 0.70, 95% CI 0.29 to 1.68); at 30 days, the mortality rate was 0.83% versus 1.21%, respectively (OR 0.72, 95% CI 0.56 to 0.94); at six months, the mortality rate was 1.92% versus 2.33%, respectively (OR 0.85, 95% CI 0.68 to 1.07); and at one year, the mortality rate was 2.61% versus 3.32%, respectively (OR 0.80, 95% CI 0.64 to 1.00). The number needed to treat at 30 days to save one life was 296. The mortality benefit appeared to dissipate by six months and was of borderline significance at one year. The incidence of MI in the treatment group compared with the control group was reduced at seven days (4.31% versus 6.97%, respectively; OR 0.59, 95% CI 0.46 to 0.75), at 30 days (4.54% versus 6.46% respectively; OR 0.63, 95% CI 0.54 to 0.74) and at six months (5.73% versus 8.29%; OR 0.65, 95% CI 0.55 to 0.77). Repeat revascularization procedures were also significantly lower in the GP IIb/IIIa group compared with the control group at seven days (2.47% versus 4.44%, respectively; OR 0.43, 95% CI 0.29 to 0.84), at 30 days (3.44% versus 5.19%, respectively; OR 0.66, 95% CI 0.56 to 0.77) and at six months (15.21% versus 17.40%, respectively; OR 0.86, 95% CI 0.78 to 0.94). Overall, the composite of death, MI and repeat revascularization was reduced at all time points. An assessment of risk revealed that the incidence of thrombocytopenia (OR 1.41, 95% CI 1.10 to 1.81) and minor bleeding (OR 1.80, 95% CI 1.47 to 2.21), but not major bleeding (OR 1.29, 95 CI 0.98 to 1.68), was significantly increased in the GP IIb/IIIa group versus the control group. Treatment with GP IIb/IIIa inhibitors in the setting of PCI significantly reduces the rates of 30-day mortality, MI and repeat revascularization procedures. These beneficial effects are achieved at an increased risk of thrombocytopenia and minor bleeding, but not major bleeding.