The widespread use of aspirin and angiotensin converting enzyme (ACE) inhibitors in patients with coronary artery disease contributes significantly to the reduction in morbidity and mortality from this common health problem. These agents are widely and concomitantly used, and they share mechanisms that may interact in negative or positive pathways. Data derived from in vitro preparations, animal studies, human studies, and case-control studies are inconsistent. No study has established firm evidence regarding the safety or adverse effect of aspirin on patients who are on ACE inhibitors. The efficacy and safety of aspirin in combination with ACE inhibitors has been questioned and debated. If a negative interaction does exist, it will affect daily practice in treating patients with coronary artery disease and heart failure. This article reviews the available data regarding the safety of combined aspirin and ACE-inhibitor treatment among patients with ischemic heart disease, to assess the possible interaction between the two drugs and to discuss thesignificance and implications of the data.