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Background: Ankle–foot pain is a significant public health problem in nurse professionals and has great burdens to the individuals, healthcare systems, and community at large. However, there is limited evidence on the prevalence of ankle–foot pain and its associated factors among nurses in Ethiopia. Thus, the finding of this study will help to address health problems resulting from ankle–foot pain among nurses. Purpose: The aim of this study was to determine the prevalence and associated factors of ankle–s–foot pain among nurse working in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia. Patients and Methods: An institutional-based cross-sectional study was conducted on a total of 366 nurses, and a simple random sampling technique was used to recruit study participants. Data were collected by using a self-administered adapted standardized Nordic questionnaire. Descriptive statistics and a bivariate logistic regression model were done to identify factors associated with ankle–foot pain. Those variables with a P-value less than 0.05 with 95% CI in multivariate model were taken as statistically significant. Finally, AOR with 95% confidence interval at a P-value of < 0.05 was reported. Results: The prevalence of self-reported ankle–foot pain among nurses was 43.7% (95% CI=38.5– 49.1). Older age (AOR=7.669, 95% CI=2.316− 25.390), low shoe comfort (AOR=4.215, 95% CI=2.031– 8.745), multiple foot conditions (AOR=6.102 95% CI=1.959– 19.008), working night shifts (AOR=2.047, 95% CI=1.098− 3.816), high physical demand (AOR=3.487, 95% CI=1.988– 6.116), and nurses working in the intensive care unit (AOR=2.402, 95% CI=1.219– 4.732) showed a statistically significant association with ankle–foot pain. Conclusion: This study indicated that the prevalence of ankle–foot pain is commonly reported among nurses working in Ayder Comprehensive Specialized Hospital. Therefore, awareness and prevention of ankle and foot pain in nurses should be prioritized to reducing risk factors. Nurses should give attention to comfortable footwear, and further longitudinal research is recommended. [ABSTRACT FROM AUTHOR]