Background: Coronary artery disease and myocardial infarction (MI) are major causes of patient morbidity, hospital mortality, and out-of-hospital sudden death. The precise location of culprit lesions in acute MI at autopsy has not been reported. Objective: The purpose of this retrospective histopathologic autopsy study was to determine the distribution of coronary culprit lesions in acute fatal MI. Methods: Cross-sections of epicardial coronary arteries were evaluated microscopically. For each culprit lesion, its distance from the coronary ostium and its grade of luminal stenosis were recorded. Results: The study group included 41 nondiabetic patients (mean age of 65 years, 66% males) who underwent autopsy at Mayo Clinic Rochester (1994-2005). Culprit lesions occurred within the proximal 3.0 cm of the left anterior descending artery in 86% and the left circumflex artery in 100%. In contrast, culprit plaques within the right coronary artery (RCA) were distributed evenly throughout its length. Conclusions: Among nondiabetic patients with acute fatal MI, culprit lesions exhibited proximal clustering in the left anterior descending artery and left circumflex artery, in contrast to more uniform distribution in the RCA. Thus, for the autopsy investigation of sudden death, evaluation for culprit lesions in the entire length of the RCA, not just its proximal region, is recommended.