ABSTRACT: INTRODUCTION:Work-related stress causes poor quality of nursing care and increases the risk of medical errors. Research evidence is so limited to nurses' work-related stress in eastern Ethiopia. Therefore, this study aimed to assess work-related stress and associated factors among nurses working in governmental hospitals in Harar, Eastern Ethiopia. METHODS:Institution-based quantitative cross-sectional study was conducted among 367 nurses from 15th to 30th March, 2015. Simple random sampling technique was applied to recruit study participants. Data were collected using structured self-administered questionnaire. Descriptive statistics, bivariate and multivariate logistic regressions were carried out. The statistical association was declared using adjusted odds ratio at 95% confidence interval (CI) and P-value of less than 0.05. RESULTS:A total of 398 study participants were involved in the study, and the response rate was 92.2% (367/398). More than half of 202(55%) of the participants were males. One third (33.8%, n = 124) of study participants' age ranged between 26 to 34 years. The prevalence of work-related stress in the current study was 66.2%. Nurses, who reared child (AOR = 2.1, 95% CI: 1.2, 3.7), working in intensive care units (AOR = 4.5, 95% CI: 1.4, 17.7), work on rotation (AOR = 2.5, 95% CI: 1.4, 4.4), and nurses who had a chronic medical illness (AOR = 2.6, 95% CI: 1.2, 5.7) were significantly associated with nurses' work-related stress. CONCLUSION:Two-thirds of nurses who were working at government hospitals had work-related stress. Work-related stress was associated with child-rearing, working units, work on rotation, and chronic medical illness. We suggested the hospital's administration, and other concerned stakeholders should design a strategy to undertake necessary measures such as hiring more nurses to minimize workload and rescheduling work shift to alleviate work-related stress among nurses.