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Abstract Background Tobacco use is the leading preventable cause of death worldwide. Besides cigarette smoking, waterpipe and e-cigarettes are gaining popularity among young adults. Medical students’ smoking behavior is of particular interest because of their impending role in health promotion as future physicians. Aim of our study is to examine the prevalence and predictors of cigarette, waterpipe and e-cigarette use and the association of tobacco use with self-reported health status in an international sample of medical students. Methods In a multicenter cross-sectional study data on different aspects of health behavior were collected from medical students of 65 nationalities using a self-administered questionnaire in Germany (Dresden, Munich) and Hungary (Budapest, Pécs). The survey was conducted among 1st, 3rd and 5th year students. To explore associations between smoking behavior and socio-cultural factors Pearson’s chi2-tests and multivariate binary logistic regression analyses were performed. Results The largest subpopulations were formed by German (n = 1289), Hungarian (n = 1055) and Norwegian (n = 147) students. Mean age was 22.5 ± 3.3 years. Females represented 61.6% of the sample. In the whole sample prevalence of cigarette smoking was 18.0% (95% CI 16.6–19.4%), prevalence of waterpipe use was 4.8% (95% CI 4.0–5.7%), that of e-cigarette 0.9% (95% CI 0.5–1.2%). More males (22.0%) than females (15.5%) reported cigarette smoking. The lowest prevalence of cigarette smoking was found among Norwegian students (6.2%). Cigarette smokers were older, waterpipe users were younger than non-users. E-cigarette use was not associated with age of the students. Religious involvement was protective only against cigarette smoking. Financial situation showed no association with any kind of tobacco consumption. Cigarette smokers and e-cigarette users were less likely to report very good or excellent health status. Conclusions Cigarette smoking is still the most popular way of consuming tobacco, although alternative tobacco use is also prevalent among medical students. To further health consciousness, medical schools should pay more attention to students’ health behavior, especially their smoking habits. Tobacco prevention and cessation programs for medical students should consider not only the health risks of cigarette smoking but the need to discourage other forms of tobacco use, such as waterpipe.