Introduction: Glycoprotein 2b/3a receptor antagonists (Gp 2b/3a) were once widely used during PCI. However, due to concerns for excess bleeding, the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization downgraded their use during PCI to Class IIa. Hypothesis Higher rates of Gp 2b/3a use will be associated with higher bleeding rates, particularly in hospitals that use more femoral arterial access. Methods: We investigated the prevalence of Gp 2b/3a use during PCI among 18 PCI centers in a regional cardiac quality collaborative, between January 2017 and June 2021. Since radial access has lower bleeding rates than femoral access, we determined the impact of Gp 2b/3a use on total bleeding as defined by NCDR, stratified by access site. Results: During the study period 36,975 PCI were performed. The rate of Gp 2b/3a use among PCI centers ranged from 2.6% to 59.3% (mean ± SD 20.5% ± 18.5%). PCI centers were analyzed according to whether Gp 2b/3a use was above or below the mean frequency, and according to arterial access site preference (femoral > 45% or radial > 55%). Among low Gp 2b/3a use centers, centers that also favored radial access had lower bleeding rates than high femoral access centers (1.84% vs 2.43%, p=0.009). However, the bleeding risk benefit of radial access was lost in the high Gp 2b/3a usage hospitals, with bleeding rates of 4.54% in the high radial centers versus 3.41% in the high femoral centers (p<0.001) (Table). Among high radial access site centers, the rate of bleeding was 2.5-fold greater in high versus low Gp 2b/3a use centers (p<0.001). Conclusions: There is a wide range of Gp 2b/3a use during PCI. Above average Gp 2b/3a use increased total bleeding and neutralized the bleeding risk benefit of radial access. Further study is required to determine why bleeding rates in high radial centers were greater than high femoral centers, when Gp 2b/3a use was above average. Adherence to current guidelines for Gp 2b/3a use may reduce bleeding risk during PCI.