The objective of this study was to evaluate the effectiveness of two different closure devices in patients undergoing rescue percutaneous coronary intervention (PCI) using IIb/IIIa inhibitors and to compare it with patients undergoing elective PCI. One hundred sixty-two patients undergoing rescue PCI treated with IIb/IIIa inhibitors underwent vascular access site closure (6 Fr Perclose, n = 92, or 6 Fr Angioseal, n = 70). Vascular complications were compared with a sex- and age-matched group (n = 100) of patients undergoing manual compression after sheath removal and a similar group of patients undergoing elective PCI (n = 196). The incidence of access site complications was not significantly different between the three groups undergoing rescue PCI and was not higher than in patient receiving GP IIb/IIIa inhibitors without fibrinolysis (RR = 0.95; 95% CI = 0.88-1.01). In patients undergoing rescue PCI and receiving IIb/IIIa inhibitors, closure devices allow early sheath removal and are associated with similar outcomes compared with manual compression and elective PCI regardless of the type of closure device used.