Introduction: This study sought to determine the sociodemographic and behavioral factors associated with water pipe and smokeless tobacco (SLT) use among a population of medical students in the Pretoria area, South Africa. Methods: Undergraduate medical students (N = 722) in their 2nd and 6th year of study in 2 medical schools in South Africa completed a self-administered questionnaire during 2008. Information on ever and current use of water pipe and SLT was obtained along with information on sociodemographic variables, alcohol use, and cigarette smoking status. Multiple logistic regression analysis were used to determine factors associated with current use of water pipe and SLT. Results: The mean age of study participants was 23 years. Of the participants, 53% were female and 55% were self-identified as Black Africans. Of the study participants, 18.6% were current water pipe users, 3.1% were current SLT users, while 17.3% were current cigarette smokers. Factors independently associated with current water pipe use were having an alcohol drinking-problem (odds ratio [OR] = 2.43; 95% CI = 1.48-3.40), currently smoking cigarettes (3.40; 2.04-5.67), and reporting exposure to smoking in places other than home (2.51; 1.29-4.90). Compared with Black students, White medical students were more likely to have smoked a water pipe in the past month (3.14; 1.74-5.70) but less likely to have ever used SLT (0.37; 0.19-0.73). Conclusions: These findings suggest that the use of alternative tobacco products is common among South African medical students and may form part of a pattern of risk-taking behavior. Furthermore, there appear to be cultural differences in the use of certain tobacco products.