A facility-based cross-sectional study was conducted among 478 randomly selected nurses working in public hospitals in eastern Ethiopia from July 15 to August 20, 2022. Data were collected through self-administered structured questionnaires and observations. Descriptive statistics was done using frequency, percentage, mean and standard deviation to summarize the study variables. Bivariate and multivariable logistic regression analysis was done to determine factors associated with the practice of surgical site infection prevention and a p-value <0.05 was used to declare a statistically significant association. Nurses’ surgical site infection prevention practice was poor and several modifiable factors were identified. Continuous in-service training on and consistent utilization of infection prevention guidelines, provision of adequate wound care supplies and close supervision are recommended to improve the practice of preventing surgical site infections.