Background: In African countries including Ethiopia occupational exposure of needle stick and sharp injuries is higher than elsewhere and it is still a major public health problem. It accounts for 86% of all occupationally related infection transmissions; expose Health Professionals to more than 20 blood borne pathogens. In Dire Dawa, Ethiopia, the magnitude of needle stick and sharp injuries and its health impacts remain unknown. In addition, available statistics underestimate the severity of the problem because most health care workers do not report their injuries. Objective: To determine the prevalence and associated factors of needle stick and sharp injuries among health care workers of public health facilities, Dire Dawa. Methods: A facility based cross sectional study was conducted using quantitative methods on a samples of 305 health care workers from five selected health facilities of Dire Dawa. Results: Both the life time and the last 12 months prevalence of NSSI were 149(53.8%) and 75(26.6%), respectively. The prevalence of NSSIs among clinical nurses, laboratory technologist and midwifery was 57%, 46% and 20%, respectively. Among the 75 cases occurred in the last one year, 49(65.3%) did not report the incident due to absence of reporting protocol (53.1%), fear of isolation and/or discrimination (20.4%), too busy to report (16.3%) and that it was not important to report the incident (10.2%). Although 80% HCWs took HBV vaccine, only 45% completed the full dose. Both before (crude analysis) and after the results were adjusted for selected variables, profession of medical laboratory (p=0.037), sometimes use of personal protective equipment (p=0.001), sometimes recapping needles after use (p=0.001), inadequate availability of post exposure prophylaxis (p=0.011), and working more than 40 H a week (p=0.009)} were factors significantly associated with occupational exposure NSSI. Conclusion: This study revealed high prevalence of NSSIs in the study area. This suggests distribution of adequate safety materials and prophylaxis is mandatory. Exposure prevention among the HCWs must be all health facilities concern and completion of three doses of Hepatitis B must be reiterated. More importantly distribution of syringe and needles which sheath or retract after use, and replace the older one, can be cost effective intervention strategy.