Background: The Self-Care of Heart Failure Index is an empirically tested instrument to measure self-care of heart failure patients across different populations and cultures. Aims: To develop and evaluate the psychometric properties of the Nepali Self-Care of Heart Failure Index. Design: This psychometric study used a cross-sectional, observational, study design to collect data. The study was guided and reported following the Strengthening the Reporting of Observational Studies in Epidemiology guideline. Methods: To develop and culturally validate Nepali Self-Care of Heart Failure Index, a combination of the recommended methods for cross-cultural validation studies were applied such as translation, back translation, expert committee review of the translated version and validity/reliability testing. Face and content validity were ensured using expert review. Construct validity was examined using exploratory factor analysis and confirmatory factor analysis. Composite reliability scores were calculated for each sub-scale of the Nepali Self-Care of Heart Failure Index. Results: A total of 221 heart failure patients in Nepal were enrolled in the study. Adequate face and content validity were ensured through expert review. Exploratory factor analysis and confirmatory factor analysis supported the original three-factor model. Although the three factors explained only 41% of the variance, confirmatory factor analysis fit indexes and error measures were found reasonable. The composite reliability coefficients for self-care maintenance, management and confidence scale were 0.6, 0.7 and 0.8, respectively. Conclusions: The Nepali Self-Care of Heart Failure Index is a theoretically based, culturally acceptable and appropriate instrument for use among Nepali heart failure patients. However, further studies are needed to refine its psychometric properties. Relevance to clinical practice: Access to reliable, valid and culturally appropriate instruments is crucial in describing the state of the problem as well as for developing and evaluating tailored and targeted self-care practice interventions for Nepali patients living with heart failure.