In the past numerous analyses have studied several aspects of autopsies in particular with regard to the decline of frequency; however, long-term studies spanning more than one decade have rarely been published, especially in recent years. On the occasion of the 100 year jubilee the archive data of the Institute of Pathology of the University of Mainz were analyzed for autopsies performed between 1971 and 2010. In this cohort, we focused on patients over 14 years old (n = 14,724) who died in the University hospital. We compared the number of autopsies with the total number of deceased patients and, in addition, studied several epidemiological aspects with special relevance for the cause of death (COD). In 1973 the peak autopsy frequency was reached with a value of 73.4 % followed by a decrease to 49.1 % in 1980. In the following decade a relatively steady state was achieved (frequency 53.3 % in 1985, and 43.2 % in 1990), followed by a remarkable decline after the 1990s (1997: 26.4 %, 1998: 15.9 % and 2010: 5.6 %). The mean overall age increased during the observation period (59.1 years in 1971 and 67.5 years in 2008). Among the COD groups cardiovascular diseases were predominantly recorded (between 35 % in the 1970s and 39 % in 1995-2010), followed by infectious diseases (between 20 and 25 %). Malignancies represented the third most common COD group with an increase in frequency from approximately 10.5 % in the 1970s to 17 % observed in the last decade. Among the single specific CODs, pulmonary embolism was most often encountered in the 1970s (about 11.5 %), while in the following decades myocardial infarction predominated (up to 15.8 % between 1995 and 2010). In the overall period, lung cancer was the single most common malignancy of the CODs (between 2.5 and 3.9 %). These data confirmed previous studies showing that in Germany the autopsy frequency began to decline remarkably in the 1990s. Besides general aspects, the specific local causes for these phenomena are discussed.