Methadone has a long and successful history in the treatment of opioid addiction. In recent years, it has become popular again—as potent and inexpensive analge- sic in patients with chronic pain. Since methadone has been used fatalities have been reported. In our study all methadone-associated deaths in Zurich from 1998 to 2007 were analysed. Most of the 146 detected deaths of the past 10 years occurred during substitution programmes or illicit intake of methadone while only three of them could be attributed to methadone used as an analgesic. Noticeable in our study was the high percentage of cases of combined drug intoxication (76%). The most frequent co-intoxicants were alcohol and cocaine. Mortalities attributed to metha- done intoxication alone were a rare finding and could only be detected in five cases of deceased who had received methadone maintenance treatment. The aim of our study is to assess the trends in the number and nature of methadone- related fatalities in Zurich during the last 19 years. For this purpose a previous study from Zurich (1989–1997) was included, whereby a very long observation period and large number of cases resulted.