Purpose <p>Ensuring cultural equivalence of measurement tools for comparability across settings, populations, and languages is a challenge for global health research. Development of a guide to interpret the meaning of dimensions within tools is an important but neglected part of transcultural translation. Our objective was to transculturally translate the EuroQol Research Foundation’s EQ-5D-5L in Nepali and develop an interpretation guide for Nepal.</p> Methods <p>The EQ-5D-5L was translated into Nepali using modified guidelines from the EuroQol Version Management Committee. We conducted forward translations (<i>n</i> = 2), backward translations (<i>n</i> = 3), and cognitive debriefing interviews (<i>n</i> = 26; 13 female; 17–72 years old).</p> Results <p>Cognitive debriefing demonstrated different understandings of EQ-5D-5L dimensions and severity rankings by age and gender. Younger adults interpreted mobility as exercise, working age adults as movement needed to complete livelihood tasks. Usual activities were interpreted by female respondents as household obligations, and by men as work outside the home. Younger adults interpreted anxiety and depression as occurring due to life dissatisfaction. Older adults described anxiety as occurring due to physical or emotional pain or unfulfilled desires, and depression due to grief. One shortcoming of the tool was its timeline being restricted to the current day.</p> Conclusion <p>Based on these interpretations, a guide was created with indicator meanings according to gender and age. Given the differences in interpretation, cost effectiveness analysis with EQ-5D-5L would benefit from age and gender specific analysis. Ultimately, developing an interpretation guide can facilitate contextualized understandings of transculturally adapted instruments in global health.</p>