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To determine the proportion of clinical errors by comparing clinical and pathological diagnoses, and to evaluate changes of errors over time.We conducted a prospective study of all consecutive autopsies performed on patients who died in the intensive care unit of the Hospital Universitario de Getafe, Madrid, Spain, between January 1982 and December 2007. The diagnostic errors were classified in two categories: class I errors that were major misdiagnoses with direct impact on therapy, and class II diagnostic errors which comprised major unexpected findings that probably would not have changed therapy.Of 2,857 deaths during the study period, autopsies were performed in 866 patients (30.3%). Autopsy reports were available in 834 patients, of whom 63 (7.5%) had class I errors and 95 (11.4%) had type II errors. The most frequently missed diagnoses were pulmonary embolism, pneumonia, secondary peritonitis, invasive aspergillosis, endocarditis and myocardial infarction. The autopsy did not determine the cause of death in 22 patients (2.6%). Our rate of diagnostic discrepancy remained relatively constant over time, and the conditions leading to discrepancies have slightly changed, with pneumonia showing a decline in diagnostic accuracy in the last years.This study found significant discrepancies in 18.5% of patients who underwent autopsy, 7.5% of them were diagnoses with impact on therapy and outcome. This reinforces the importance of the postmortem examination in confirming diagnostic accuracy and improving the quality of care of critically ill patients.