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Abstract Nurses play a key role in medication safety and, by extension, patient safety. Evaluation of medication safety competence in nurses requires valid, specific, and comprehensive instruments. The present study was conducted to translate and psychometric assessment a Persian version of medication safety competence scale (MSCS) for clinical nurses in Iran. This is a cross-sectional and multi-centric work of research with a methodological design. A total of 1080 clinical nurses were selected from 5 cities located in Iran. The original version of the MSCS was translated into Persian and the psychometric properties of MSCS were assessed using COSMIN criteria. The exploratory factor analysis (EFA) showed that the factor loading of the 36 items was between 0.72–0.87, all of which were significant. The confirmatory factor analysis (CFA) fitted the data well (χ2/df = 7, RMSEA = 0.01, CFI = 0.96, NFI = 0.95, and TLI = 0.97). The reliability of the instrument was assessed in terms of its internal homogeneity where the Cronbach's alpha of the whole instrument was found to be 0.96. The Persian version of MSCS for nurses possesses satisfactory validity and reliability. Thus, nurse managers can use this instrument to measure medication safety competence in nurses.