This is a retrospective review of occupational exposure to human immunodeficiency virus (HIV) and subsequent postexposure prophylaxis (PEP) among healthcare workers (HCWs) in King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand. From January 2002 to December 2004, data were collected from incident reports, the hospital's infectious diseases unit and the emergency department. There were 315 reported episodes of occupational exposure among 306 HCWs. Nurses (34.0%) were the HCWs most frequently exposed and percutaneous injury (91.4%) was the most common type of exposure. One-third of the source patients tested were infected with HIV. PEP was initiated following 200 (63.5%) of the 315 exposures and was started within 24h in >95% of cases. The most commonly prescribed PEP regimen was zidovudine, lamivudine and nelfinavir. Fifty-six percent of HCWs given PEP completed a four-week course but the remainder discontinued PEP prematurely due to side-effects, or after negative results from the source, or following informed risk reassessment or from their own accord. No exposed HCW acquired HIV during the study period. Appropriate counselling and careful risk assessment are important in achieving effective HIV PEP among HCWs.