Background While treatment for HIV has greatly improved patient outcomes, health care workers, including nurses, remain at high risk of occupational exposure. The risk of exposure is a continuous concern in the South African health system that is overburdened by multiple stressors, including the highest HIV caseload in the world. The aim of this study was to estimate the prevalence of occupational exposure to HIV, reporting and utilization of post-exposure prophylaxis, knowledge, attitudes towards HIV post-exposure prophylaxis and infection control practices amongst nurses at a tertiary hospital in the Western Cape, South Africa. Methods A cross-sectional study was conducted at Tygerberg hospital from the 4 th to the 16 th February 2019. Participants were front line nurses working in randomly selected wards. A selfadministered questionnaire was used to collect data from participants. Results Of the 160 participants who took part in the survey, 17 reported occupational exposure to HIV (prevalence 10.6%, 95% CI 6.7-16.6), and of the 17 exposed, 10(58.8%) reported needlestick injuries. From those who were exposed, only 10 (58.8%) reported the incidents and went on post-exposure prophylaxis. However, only 6 out of the 10 completed their treatment. Half (50%) of the participants had inadequate knowledge on HIV post-exposure prophylaxis, 83.3% had adequate attitudes towards HIV post-exposure prophylaxis and 75% had adequate infection control practices.