Introduction: Occupational injuries in medical students are concerning, especially in countries with a high prevalence of bloodborne infections. With more HIV-infected patients on antiretroviral treatment, appropriate post-exposure prophylaxis (PEP) depends on knowledge of source patients' infection status and treatment response. This study determined the number and type of exposure incidents, reporting practices, and PEP use among medical students at the University of Pretoria, South Africa. Methodology: Data were collected from an anonymous voluntary questionnaire completed by medical students from years 1 to 6 of study as well as from incident records archived at the Department of Family Medicine. Data were described and tests of association performed in Stata 11. Results: Thirteen percent of students overall and 21% of senior students reported an incident in the preceding year. The majority of incidents occurred during phlebotomy, with fatigue and work pressure found to be major contributing factors. Underreporting was common and many students displayed a lack of risk awareness and a preference for managing the incident privately. Although 59% knew the HIV-status of the source patient, less than a third knew the viral load and only 16.9% the regimen. Side-effects on antiretroviral treatment used for PEP were common and only about three-quarters of the students completed the course. Conclusions: We recommend targeted training, especially in the senior years, together with improving the work environment through attention to working hours, sharps disposal and ready availability of safety devices, improved reporting systems, individualised PEP, and possibly the implementation of an occupational injury support line.