Background: Health professional students frequently use alcohol and narcotics. The potential impact on academic performance and professional behaviour is concerning.Aim: This study aimed to determine self-reported use of alcohol, illicit substances (e.g. cannabis, lysergic acid diethylamide [LSD], magic mushroom, cocaine, crack, ecstasy, methamphetamine and heroin), prescription medication and smoking habits, correlating academic performance.Setting: Faculty of Health Sciences, University of the Free State.Methods: An observational, descriptive, cross-sectional study design was used. Information was obtained using a self-administered questionnaire, capturing demographics, self-reported academic performance, drinking and smoking habits, and substance use. Coded responses were analysed using the Remark Office OMR 8 Software System. Descriptive statistics were calculated for categorical variables.Results: Completed questionnaires comprised 171 students. A total of 78.4% of second year and 82.8% of third year students reported using alcohol. Twenty-two per cent of second year and 24.1% of third year students reported cannabis use. In the second year group, three (2.7%) students reported using magic mushroom, two (1.8%) reported cocaine, two (1.8%) reported ecstasy and one (0.9%) reported using methamphetamine. Only third year students reported using LSD or ‘crack’. Cigarette smoking was common – 31.5% and 35.1% in both groups, respectively. Smokeless tobacco devices were used by 8.5% of second year and 7.1% of third year students. Almost 40% of both groups reported that they had smoked a water pipe. Academic performance achieved was mostly 60% – 69% (38.9%) among second year students and 70% – 79% (46.6%) among third year students.Conclusion: Self-reported use of alcohol and drugs and smoking among medical students is alarming. Additional student support, early identification and referral for management and/or rehabilitation should be a priority at tertiary institutions responsible for training future healthcare professionals.