Angiotensin-converting enzyme (ACE) inhibitor use in patients at high risk of coronary artery disease has been associated with a decrease in the risk of myocardial infarction (MI) and death. However, it is unclear whether chronic use of these agents modifies the course and outcome of an acute coronary syndrome (ACS). This study assessed the association between chronic use of ACE inhibitors and clinical outcomes in patients with ACS. From 1999 through 2008, 13,632 Canadian patients with ACS were identified in the Global Registry of Acute Coronary Events (GRACE), the expanded GRACE (GRACE(2)), and the Canadian Registry of Acute Coronary Events (CANRACE). Patients were stratified by previous use of an ACE inhibitor. Clinical characteristics, in-hospital treatment, and outcomes were compared between the 2 groups. Multivariable logistic regression analysis adjusting for GRACE risk score and other clinical factors was performed. Patients receiving an ACE inhibitor before the ACS had a higher prevalence of diabetes (40.6% vs 21.2%, p <0.001), previous MI (51.8% vs 23.3%, p <0.001), heart failure (18.0% vs 6.9%), and higher GRACE scores at presentation (133 vs 124, p <0.001). Multivariable analysis demonstrated no significant association between previous ACE inhibitor use and death (adjusted odds ratio [OR] 1.15, confidence interval [CI] 0.90 to 1.49, p = 0.27), in-hospital re-MI (adjusted OR 0.99, CI 0.78 to 1.25, p = 0.91), or the composite end point of death/re-MI (adjusted OR 1.01, CI 0.84 to 1.20, p = 0.94). In conclusion, previous use of an ACE inhibitor is not independently associated with improved in-hospital outcomes after an ACS.