Background: Needle-stick injuries (NSIs) and splash exposures carry a risk of occupational acquisition of HIV and other blood borne pathogens to healthcare workers (HCWs) involved in clinical care. This study was carried out to determine the frequency and factors contributing to NSIs and splash exposures as well as post-exposure practices among HCWs in our centre. Methods: This was a cross-sectional study among healthcare workers which was conducted at Bugando Medical Centre (BMC) over a one-year period between April 2013 and March 2014. Results: Out of 436 HCWs who participated in this study, 212 (48.6%) reported incidents of NSIs and splash exposures within the previous 12 months. NSIs were reported by 65.1% (n= 138) and splash exposures by 27.4% (n = 58). Sixteen (7.5%) respondents had both NSIs and splash exposures. High rates of NSIs were observed among nurses (71.0%), during procedures (53.6%) and occurred commonly in the Accident and Emergency department (33.3%). Hollow bore needles were responsible for 63.8% of NSIs. Splash exposures occurred more commonly in operating theatre (41.4%). At the time of the exposure, 116 (54.7%) HCWs wore protective equipment. The most common action following exposure was washing the site with soap and water (55.6%). Only 68 (32.1%) reported the incident of exposure to the relevant authority. Healthcare workers aged ≤ 40 years; those with work experience of ≤ 5 years and those not trained on issues related to infection prevention and occupational risk reduction were more likely to be exposed to any type of occupational injuries studied. While male healthcare workers were less likely to be exposed to NSIs, female were more likely to encounter both NSIs and mucocutaneous splashes (p < 0.001). The majority of HCWs, 185 (87.3%) were not adequately immunized for hepatitis B virus and only 17 (8.0%) were fully vaccinated, having received three doses of the vaccine. Only 16.7% of exposed HCWs received post-exposure prophylaxis for HIV. Subsequent six-month follow-up for HIV showed zero seroconversion. Conclusion: NSIs and splash exposures are common among HCWs at our centre and are under-reported. Post-exposure management is generally poor. All HCWs should be trained on issues related to infection prevention and occupational risk reduction. The hospital should establish surveillance system for registering, reporting and management of occupational injuries and exposures.