Background <p>The prevalence of psychosocial risk factors and disability are increasing in Nepal calling for biopsychosocial tools for evaluation of musculoskeletal pain and prediction of risk factors. Örebro Musculoskeletal Screening Questionnaire (OMSQ) is a 21-item tool that is used to identify patients at risk of developing disability from nonspecific musculoskeletal pain conditions. The purpose of this study was to translate OMSQ, validate and test the reliability of the Nepali version of the OMSQ in both the urban and rural population.</p> Methods <p>OMSQ was translated into Nepali according to Beaton and tested for validity and reliability in urban and rural clinics by adult persons with chronic non-specific musculoskeletal pain (<i>n =</i> 147). Internal consistency was calculated by Cronbach’s alpha and test–retest reliability was evaluated by intraclass correlation coefficient, ICC. Responsiveness using a ROC curve was used to estimate sensitivity and specificity to detect a change in OMSQ between the test and retest. Floor and ceiling effects of the OMSQ scores were analyzed. The experience with OMSQ was surveyed with closed- and open-ended questions. The narratives were assessed with categoric content analysis.</p> Results <p>Meaning and measurement properties of Nepali OMSQ were retained when translated into Nepali and found reliable (ICC &gt; 0.75) and valid for use in both urban and rural settings in Nepal showing high internal consistency (Cronbach’s alpha urban pre-post; 0.790 and 0.768, rural pre-post; 0.827 and 0.783). ROC showed good responsiveness for urban and rural, area under curve (AUC) 0.751 and 0.760 respectively). Total scores were evenly distributed without floor or ceiling effects. In general, OMSQ was considered easy/moderate to understand/complete, though respondents in the rural sample needed more time to complete. Some of the participants had difficulties with long words and understanding of the Likert-scale.</p> Conclusion <p>OMSQ was successfully translated to Nepali and found to be a reliable and valid instrument for assessing psychosocial parameters associated with nonspecific musculoskeletal pain across diverse settings in Nepal.</p> Trial registration <p>Not applicable.</p>