Introduction and objectives: For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF. Methods: Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis. Results: Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P =.012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF > 40% (P value for treatment-by-LVEF interaction =.008). For patients with LVEF > 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P =.031). Conclusion: The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF > 40% and ST-segment elevation myocardial infarction. In non–ST-segment elevation-ACS patients with LVEF > 40%, further studies are needed to assess the prognostic impact of ACEI/ARB. © 2019