Background: Given differences in prior trial designs, the treatment tradeoffs between bivalirudin and heparin in patients with STEMI undergoing PCI remain uncertain. Study-level meta-analyses lack granularity to provide conclusive answers or assess subgroups.Methods: We performed an individual-patient-data pooled analysis from all 6 large (n>1000) RCTs of bivalirudin vs heparin in STEMI pts undergoing PCI (BRIGHT, EUROMAX, HEAT-PPCI, HORIZONS-AMI, MATRIX, and VALIDATE-SWEDEHEART). The primary efficacy outcome was the 30-day rate of all-cause mortality. Subgroup analyses were performed according to planned use of glycoprotein IIb/IIIa inhibitors (GPI), and administration of a post-PCI bivalirudin infusion.Results: A total of 15,254 patients with STEMI undergoing PCI were included (7,306 randomized to bivalirudin and 7,948 to heparin [43.6% with planned GPI use]). Thirty-day mortality was not significantly different between bivalirudin vs heparin (aHR: 0.80; 95% CI: 0.64, 1.01); 30-day cardiac mortality was reduced with bivalirudin (aHR: 0.72; 95% CI: 0.57, 0.91). There was a higher risk of 30-day MI (aHR: 1.29, 95% CI: 1.02, 1.64) and stent thrombosis (aHR: 1.42; 95 % CI: 1.05, 1.91) but lower risk of serious bleeding (aHR: 0.57 (0.47, 0.68) with bivalirudin vs heparin. At 1 year, net adverse clinical events were reduced with bivalirudin (aHR: 0.84; 95% CI: 0.77, 0.93) (Table). All-cause mortality was reduced with bivalirudin when a post-PCI infusion was used. A high-dose post-PCI infusion mitigated the 30-day MI and ST risks, irrespective of planned GPI use with heparin.Conclusions: In patients with STEMI undergoing PCI, procedural anticoagulation with bivalirudin did not reduce all-cause mortality. Cardiac mortality and serious bleeding were reduced with bivalirudin at the cost of increased rates of MI and ST. Full analyses will be presented at AHA 2022.