The study is designed to establish the factors associated with percutaneous /needle stick injuries among health care workers (HCWs) working in Nyangabwe Referral Hospital. Institution-based cross-sectional study design was conducted among 222 randomly selected health care workers in Nyangabwe Referral hospital. The data was collected using self-administered questionnaires. The data was entered into epi info version 7.2.2.16 for analysis and exported to Microsoft excel for visualization. The multivariate regression model was used to determine the association of variables with needle stick injuries/percutaneous injuries with AOR and 95% CI & P value ≤ 0.05. This study revealed that 57% of the health care workers in Nyangabwe referral hospital had sustained percutaneous injuries/needle stick injuries during their period of work in the hospital. Nurses were the most affected cadre. Needles, suture needles, and cannulas are the most contributors to percutaneous injuries and needle stick injuries. NSI/PI occurs mostly due to fatigue, workload, inattentiveness, and distraction. The most significant associated factors to PI/NSI were Education level, work unit, years of experience, use of IPC guidelines, work environment as well as working hours. Percutaneous injuries/needle stick injuries in this study area were prevalent. The most contributing factors to NSI/PI were work unit (medical and pediatric ward), Work environment (busy wards), hours of work (≥40 hours per week), non-utilization of infection prevention and control guidelines.