CONTEXT: Ischemic heart disease (IHD) due to coronary atherosclerosis constitutes the leading cause of morbidity and mortality worldwide. This review was undertaken to retrospectively analyze the lines of research that generated the evidence for our contemporary understanding of atherosclerosis-based coronary artery disease and to provide a rationale for continued support for autopsy-based research in order to make further progress in reduction of the morbidity and mortaility from IHD. OBJECTIVES: To analyze the contributions of the autopsy to complement and validate other lines of investigation in determining the complex interactions between coronary artery alterations linked to the major manifestations of coronary atherosclerosis, namely, coronary thrombosis, acute myocardial infarction, and sudden cardiac death. DATA SOURCES: Systematic search on PubMed to gather relevant studies concerning autopsy studies and reviews of the pathology and pathogenesis of atherosclerosis, ischemic heart disease, coronary atherosclerosis, coronary thrombosis, myocardial infarction and sudden cardiac death. CONCLUSIONS: An extensive search of the published literature has confirmed the continuing importance of the autopsy as a powerful tool to understand the pathogenesis, clinical features, and therapeutic options for the treatment of atherosclerosis and its major manifestation, ischemic heart disease. This has been described in the Part I companion of the present review. Autopsy-initiated studies have documented the prevalence and clinicopathological significance of atherosclerosis in different human populations and its relationship to risk factors. It has been shown that the clinically silent phase of ischemic heart disease (IHD) begins in the first decades of life. Pathological studies have clarified the complex relationship between coronary atherosclerosis, coronary thrombosis, and myocardial ischemic events. These studies also have elucidated the pathological basis of sudden cardiac death. Insights from these studies also have been important in developing and evaluating strategies for continued progress in reducing the morbidity and mortality attributed to atherosclerosis and IHD.