The Heart Outcomes Prevention (HOPE) trial was the first to demonstrate the benefits of the angiotensin-converting enzyme (ACE) inhibitor ramipril for high-risk cardiovascular patients. Whether the cardioprotective effects seen in HOPE and other trials are specific to distinct ACE inhibitors remains controversial. Evidence of a lack of class effect for ACE inhibitors has policy and financial implications related to reference pricing by insurers and inclusion on pharmacy formularies. Because head-to-head trials comparing the different ACE inhibitors are unforeseen, clinicians and administrators must rely on secondary-level data and observational studies. Only a handful of studies have sought to address the dispute over a class effect among ACE inhibitors, which is reviewed in this article.