The frequency of autopsies appears to be declining, and the usefulness has been challenged. We reviewed cases of autopsied active infective endocarditis (IE) during 2 periods based on the availability of high-tech 2-dimensional echocardiograms: Period 1 (P1) included 40 cases studied from 1970 to 1985, and Period 2 (P2) included 28 cases seen from 1986 to 2008--that is, before and after the introduction of echocardiograms in our institution. We conducted the study to reassess the pathology of IE and to determine how frequently diagnosis is not made during life.The age of patients increased 10 years on average between the 2 periods, and comorbidities were significantly more frequent in P2. While the frequency of rheumatic valve disease and prosthetic valve endocarditis (PVE) decreased, degenerative valve disease increased. Isolated mitral or aortic valve IE was most common. Right-sided IE was observed in patients with Staphylococcus aureus bacteremia from infected venous lines. In most cases IE involved only the cusps of cardiac valves. "Virulent" microorganisms caused ulcerations, rupture, and perforation of the cusps and necrosis of chordae tendiniae and perivalvular apparatus. In PVE the lesions were located behind the site of attachment, and vegetations were seen on the sewing ring in both metallic and biologic prostheses. Infection spread to adjacent structures and myocardium with ring abscess observed in 88% of cases. Prosthetic detachment causing valve regurgitation was associated with abscesses in 76% of cases; these patients developed persistent sepsis and severe cardiac failure. Obstruction occurred in patients with PVE of the mitral valve. Acute purulent pericarditis was observed in 22% of cases, mainly in patients with aortic valve IE and myocardial abscesses.Gross infarcts were seen in 63% of cases but were asymptomatic in most instances. The spleen, kidneys, and mesentery were the sites most frequently involved. Myocardial infarctions were found in less than 10% of cases. Abscesses were also frequently found and were a common source of persistent fever and bacteremia. Glomerulonephritis was more common in the first period. Brain pathology consisted of ischemic and hemorrhagic infarcts and abscesses. Cerebral bleeding was more frequent in patients with PVE on anticoagulant therapy. Neutrophilic meningitis was observed in S. aureus IE.Diagnosis of IE was not made during life in 14 (35%) cases during P1 and 12 (42.8%) cases in P2. Overall, diagnosis was missed until autopsy in 38.2% of cases. IE was hospital acquired in 28 instances. While a clinical diagnosis was made in all but 4 cases of early-onset PVE (23.5%), the diagnosis was not made during life in 22 of 51 patients with native-valve IE (43.1%). Of these 22 patients, IE was hospital acquired in 11 (50%). The absence of fever, cardiac murmurs, and many of the typical stigmata of endocarditis may have led to the diagnosis being overlooked clinically.Brain bleeding, cardiac failure and less frequently acute myocardial infarct were the most common causes of death.IE continues to be missed frequently until autopsy. Postmortem examination is an important tool for evaluating the quality of care, and for guiding teaching and research related to cardiovascular infections.