Background Non-occupational HIV post-exposure prophylaxis (NPEP) is prescribed following a risk exposure in an effort to reduce the risk of HIV seroconversion. We aimed to describe the prescribing practices of NPEP at RPA Sexual Health in Sydney, the prevalence and correlates of adverse events (AEs), and factors associated with completing the 28-day course. Methods: The study population included individuals prescribed NPEP during January 2008–December 2011. Correlates of AEs and course completion were assessed by logistic regression. Results: On 319 occasions during the study period, 282 individuals presented for NPEP. Over 90% of presentations followed unprotected anal intercourse between men, mostly receptive (63.6%). Tenofovir–emtricitabine–stavudine (n = 149; 46.7%) and tenofovir–emtricitabine (n = 136; 42.6%) were most commonly prescribed. AEs were reported at 101 presentations (31.7%, 95% confidence interval (CI): 26.6–37.1%), with nausea and lethargy/malaise being the most common. Younger age (P for trend = 0.032), earlier year of NPEP prescription (P for trend = 0.011), being prescribed a regimen other than tenofovir–emtricitabine (P = 0.026), changing the NPEP regimen (P