BackgroundMedication adherence is a key component of successful dialysis in end-stage renal disease (ESRD). The aim of this study was to use the Capability-Opportunity-Motivation and Behavior (COM-B) model in order to identify the most important determinants of medication adherence among ESRD patients.MethodsThis research was a cross-sectional design that was conducted in two steps in 2021. In the first step, COM-B components of patients undergoing hemodialysis (HD) therapy were extracted through literature review. The second step was a cross-sectional study among 260 ESRD patients referred to the dialysis unit from Kermanshah, in the west of Iran. Data was collected using a written questionnaire by interviews. The data was analyzed in SPSS version 16 software.ResultsThe mean age of respondents was 50.52 years [95% CI: 48.71, 52.33], ranged from 20 to 75 years. The mean score of medication adherence was 11.95 [95% CI: 11.64, 12.26], ranged from 4 to 20. Medication adherence is higher among patients with higher education (P = 0.009) and those who were employed (P < 0.001) and was significantly related to income (r = 0.176), while it was inversely and significantly related to the medication duration (r=-0.250). Motivation (Beta: 0.373), self-efficacy (Beta: 0.244), and knowledge (Beta: 0.116) are stronger determinants of medication adherence.ConclusionCOM-B model can be proposed as an integrated framework in predicting medication adherence among ESRD patients. Our findings provide theory-based recommendations that can help future clinical and research decision-making for the development, implementation, and evaluation of treatment adherence interventions in Iranian ESRD patients. The use of COM-B model can provide a comprehensive explanation about medication adherence in ESRD patients. Future research should be focus on increasing motivation, self-efficacy and knowledge of Iranian ESRD patients in order to increasing medication adherence.