Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) had beneficial effects on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) in the pre-reperfusion or thrombolytic era. It is unknown if the benefits persist in the contemporary reperfusion era.We sought to determine if ACEI/ARB improves clinical outcomes of patients with STEMI in the contemporary reperfusion era according to the reperfusion strategy.12596 patients were analyzed from the prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) Registry. These patients were classified into the no reperfusion group (n=6004) and the primary percutaneous coronary intervention (PCI) group (n=6592). Two-year all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) were compared.In the no reperfusion group, ACEI/ARB therapy at discharge may reduce the incidences of 30-day MACCE (4.7% vs 7.4%; adjusted hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.53-0.85; P<0.001), stroke (0.5% vs 1.1%; adjusted HR: 0.41; 95% CI: 0.21-0.83; P=0.01), and revascularization (2.1% vs 3.1%; adjusted HR: 0.66; 95% CI: 0.46-0.94; P=0.02) compared to patients not treated with ACEI/ARB. Patients treated with ACEI/ARB also showed a lower rate of two-year MACCE (17.0% versus 19.1%; adjusted HR: 0.87; 95% CI: 0.76-0.99; P=0.04). No differences were observed in the remaining outcomes. In the primary PCI group, no differences were observed for all examined outcomes before and after multivariate adjustments.Treatment with ACEI/ARB at discharge may reduce cardiovascular events in STEMI patients not receiving reperfusion, while no significant benefits were observed in those receiving primary PCI.