Introduction: Hospital autopsies, vanishing worldwide, need to be requested by clinicians and consented to by next-of-kin. The aim of this prospective observational study was to examine how often and why clinicians do not request an autopsy, and for what reasons next-of-kin allow, or refuse it. Methods: Clinicians at the Erasmus University Medical Centre were asked to complete a questionnaire when an adult patient had died. Questionnaires on 1000 consecutive naturally deceased adults were collected. If possible, missing data in the questionnaires were retrieved from the electronic patient record. Results: Data from 958 (96%) questionnaires was available for analysis. In 167/958 (17.4%) cases clinicians did not request an autopsy, and in 641/791 (81.0%) cases next-of-kin did not give consent. The most important reason for both clinicians (51.5%) and next-of-kin (51.0%) to not request or consent to an autopsy was an assumed known cause of death. Their second reason was that the deceased had gone through a long illness (9.6% and 29.5%). The third reason for next-of-kin was mutilation of the deceased's body by the autopsy procedure (16.1%). Autopsy rates were highest among patients aged 30-39 years, Europeans, suddenly and/or unexpectedly deceased patients, and tissue and/or organ donors. The intensive care and emergency units achieved the highest autopsy rates, and surgical wards the lowest. Conclusion: The main reason for not requesting or allowing an autopsy is the assumption that the cause of death is known. This is a dangerous premise, because it is a self-fulfilling prophecy. Clinicians should be aware, and communicate with the next of kin, that autopsies not infrequently disclose unexpected findings, which might have changed patient management. Mutilation of the deceased's body seems a minor consideration of next-of-kin, though how it really affects autopsy rates, should be studied by offering minimally or non-invasive autopsy methods.