BACKGROUND Methylphenidate hydrochloride (MPH) is used in the treatment of attention deficit hyperactivity disorder (ADHD). The non-medical use of MPH by learners and students has been reported by numerous studies from abroad. The practice stems from beliefs about the benefits of MPH in achieving academic success. Little is known about the use of MPH in South African student populations. OBJECTIVE The study set out to determine (1) the extent and dynamics associated with MPH use and (2) poly-substance use among undergraduate students attending a South African university. METHODS 818 students took part in a written, group-administered survey. Data analysis resulted in descriptive results regarding MPH use and tests of association identified differences in MPH and poly-substance use among respondents. RESULTS One in six respondents (17.2%) has used MPH in the past, although only 2.9% have been diagnosed with ADHD. Nearly a third (31.7%) of users obtained MPH products illegally. The majority (69.1%) used MPH only during periods of academic stress. A significant association (p < 0.001) was found between MPH use and the frequency of using alcohol, tobacco, cannabis, hard drugs (e.g. cocaine) and prescription medication. CONCLUSIONS MPH use among students appears similar to experiences abroad, especially in the absence of clinical diagnosis for ADHD. Institutions of higher education should inform parents and students about the health risks associated with the illicit use of MPH. Prescribers and dispensers of MPH products should pay close attention to practices of stockpiling medication and poly-substance use among students who use MPH.