INTRODUCTION: The autopsy rate has continuously diminished over the past few decades, reducing the quality of medical care and the accuracy of statistical health data. OBJECTIVE: To assess the accuracy of clinical diagnoses by comparing pre- and postmortem findings, and to identify potential risk factors for misdiagnoses. METHODS: Retrospective evaluations performed between June 2001 and June 2003 in a 2500-bed tertiary university hospital in São Paulo, Brazil, including 288 patients who died at that institution and had a postmortem examination. RESULTS: Clinical and autopsy records were reviewed and compared for categorization using the adapted Goldman criteria. The overall major and minor discrepancy rates were 16.3% and 28.1%, respectively. The most common missed diagnoses were pulmonary embolism, pneumonia, and myocardial infarction, and the most prevalent underlying diseases were infectious diseases, cerebro-cardiovascular conditions, and malignancies. Patients age 60 or older had an increased risk of diagnostic disagreement, as did female patients. The period of hospitalization, last admission unit at the hospital and underlying disease were not significantly related to the pre-mortem diagnostic accuracy. DISCUSSION: The discrepancy rate found in this study is similar to those reported globally. The factors influencing diagnostic accuracy as well as the most commonly missed diagnoses are also consistent with the literature. CONCLUSION: Autopsy remains a crucial tool for improving medical care, and effort must be focused on increasing its practice worldwide.