Background: Adherence to the treatment regimen reduces complications of surgery after heart valve replacement. Educating the patient can improve treatment adherence. This study thus aimed to evaluate the effect of education based on the health belief model (HBM) on treatment adherence in patients with heart valve replacement surgery. Methods: In this quasi-experimental research, a total of 90 patients undergoing valve replacement surgery were studied. The subjects were selected randomly and then divided into an intervention and a control group using the permutation blocks method. The data were collected using a demographic questionnaire, an HBM- based questionnaire, and a treatment adherence questionnaire during two stages before and one month after the education. Three 60-minute sessions on HBM- based education were held based on a need assessment for the intervention group. The collected data were analyzed using the chi-square test, paired t test, independent t test, and linear regression in SPSS software version 16.0. Results: Most of the patients in the two groups were male, married, and employed, had reading and writing literacy and lived in an urban area. Both groups were similar in terms of demographic data except for marital status, disease history, and familial disease history. The mean scores of knowledge, HBM constructs (e.g., perceived susceptibility, perceived severity, perceived benefits, perceived barriers, perceived self-efficacy, and cues to action), and treatment adherence were greater in the control group than in the intervention group pre-intervention. However, the mean scores of all variables improved in the intervention group, and there were significant differences in the knowledge, all HBM constructs (except for perceived susceptibility and perceived self-efficacy), and medical adherence between the two groups post-intervention (P<0.05). Conclusion: Considering the positive effect of HBM-based educational intervention on the patients’ treatment adherence, HBM-based education could be suggested for patients with heart valve replacement surgery.