This study identifies the prevalence of smoking, alcohol, and illicit drug use in a sample of Turkish medical students. Information about substance use was obtained from 304 first-year, and 143 sixth-year medical students from three different medical schools in Turkey. Nearly half of the students (53.9%) were non-drinkers. Risky alcohol use was 7.4%. Lifetime smoking prevalence was 39.9 and 26.4% of the junior and 44.1% of the senior medical students (mean consumption of 13.9 and 15.5 cigarettes a day, respectively) reported regular smoking. Nicotine dependence was present in 3.1%. Only 4% of the students reported using illicit drugs (cannabis, ecstasy, cocaine) at least once in their lifetime. The mean ages of first use of cigarettes, alcohol and illicit drugs were earlier for junior medical students than senior students. Of the students, 25.5% had anxiety and 36.8% had depression scores in the clinically significant range. Our results suggest that although Turkish medical students are not at a high risk of substance abuse it should not be underestimated, and the risk factors as well as the protective factors must be identified in nation-wide studies.