Background: In Ethiopia very limited information is available on the epidemiology of needle stick sharp injuries exposure among health professionals. This study is intended to determine the magnitude and factors associated with sharp injury among health care workers (HCWs) in public institutions in Enemorener district, Southern Nation Nationality People Region (SNNPR), Ethiopia, 2017. Methods: A cross-sectional study was conducted from August 2017 to April 2018. A total of 325 health workers were selected using stratified sampling technique. The data were collected using pretested self administered questionnaire. Data were analyzed using bivariate and multivariate binary logistic regression analysis. The outputs of the analysis are presented using adjusted odds ratio (OR) with 95% confidence interval (CI). Results: Out of the total 325 study subjects, 317 (97.5%) of them were included the final analysis. In the previous one year, nearly half (49.2%) with 95% CI of 42.2% to 54.6% HCWs had experienced at least one needle stick sharp injury (NSSI). The multivariate analysis revealed that females have 2.4 times more odds of experiencing NSSIs compared with males (AOR 2.40, 95% CI: 1.39, 4.14). Midwives had 2.95 times increased odds of experiencing NSSI as compared with the health officers (AOR 2.95, 95%CI: 1.07, 8.09). As compared to those working in the emergency unit, health professionals working at outpatient and under five units had 71% (AOR 0.29, 95% CI: 0.14, 0.61) and 82% (AOR 0.18, 95% CI: 0.07, 0.46) reduced odds of NSSI. HCWs who had no trainings on infection prevention were 2.89 times at increased odds of getting NSSIs as compared with the counterparts (AOR 2.89, 95% CI: 1.87, 4.05). Conclusion: This study demonstrated a relatively high prevalence of NSSIs among HCWs of the study area. This highlights the need for developing and implementing effective preventive strategies including training of health workers especially those working in the emergency wards