The aim of this study was to research the drug-induced mortality and characteristics of overdose deaths in the Split-Dalmatia County in the period between 1986 and 2005, and in the war (1991–1995), pre-war (1986–1990), post-war (1996–2000) and period between 2001 to 2005. We retrospectively searched through Databases of the Department of Forensic Medicine, University Hospital Split, the national register of death records, the archives of the Split-Dalmatia County Police and the Register of Treated Drug Addicts of the Croatian National Institute of Public Health, according to drug poisoning codes IX and X of the International Classification of Diseases. During the period covered by study, the absolute number and rate of deaths from drug overdose have increased significantly. Quantitative changes were most prominent in the war period (1991–1995) when rates increased almost 5 times compared with the pre-war period (1986–1990). The deceased were mostly male, middle-aged, high school educated, unmarried and unemployed with a criminal record. The largest number of deaths occurred in Split and they were usually a result of consumption of heroin, alone or in combination with other substances. The research confirmed all proven risk factors for death from an overdose of drugs have been increased due o an unfavorable war and postwar developments.