BACKGROUND: Identifying the causes and consequences of work interruptions in nursing is crucial, as they play a vital role in improving workflow, nurse well-being, and enhancing patient safety. Therefore, by considering these factors, healthcare institutions can implement effective interventions and strategies to improve the nursing work environment while simultaneously enhancing the quality of patient care. AIM: This study aims to culturally adapt and psychometrically evaluate the Persian version of the Nursing Work Interruption Scale. METHODS: This methodological cross-sectional study involved a sample of 506 nurses selected through convenience sampling. The translation and cultural adaptation of the Nursing Work Interruption Scale were conducted using the Polit and Yang model. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and assessments of internal consistency were conducted to evaluate the validity and reliability of the instrument. SPSS version 27 and LISREL version 8 software were used in this study. RESULTS: The results of the EFA and CFA confirmed the tool with two factors and 12 items. The CFA results indicated a well-fitting model (CFI = 0.91, NNFI = 0.92, GFI = 0.91, RMSEA = 0.057, SRMR = 0.045). Pearson's correlation coefficient confirmed a significant relationship between items, subscales, and the main scale. Additionally, Cronbach's alpha coefficient (0.896) and McDonald's Omega (0.892) confirmed the scale's reliability. CONCLUSION: The Persian version of the Nursing Work Interruption Scale is a valid and reliable tool, consisting of 12 items and two factors. This scale provides a valuable tool for measuring the extent of work interruptions experienced by nurses. Additionally, it can be utilized to develop and evaluate the efficacy of strategies designed to reduce these interruptions. CLINICAL TRIAL NUMBER: Not applicable.