ObjectivesMultiple sclerosis (MS) is a chronic and progressive disease that causes stress due to its unpredictability and lack of definitive treatments. This study examined the effects of an educational program using a transactional model to help women with MS cope with their disease.Materials and MethodsIn a randomized clinical trial, 80 female patients from the MS Society of Iran were randomized to the intervention (n = 40) or a control group (n = 40). Outcomes were assessed using Cohen's Perceived Stress Scale (PSS) and the Jalowiec Coping Scale (JCS), which were completed by both groups at baseline, 1 month, and 3 months after the intervention. The intervention consisted of six educational sessions administered over 2 months based on a transactional model. The data were analyzed using repeated measures ANOVA.ResultsAverage PSS scores decreased significantly over time in the intervention group, while increasing in the control group. Between‐group differences were significant at both 1‐month and 3‐month follow‐up (p < .001). Both problem‐focused and emotion‐focused coping styles improved over time in use and effectiveness in the intervention group, whereas little or no change occurred in these coping behaviors in the control group.ConclusionThe transactional model‐based education program tested here was successful in reducing stress levels and increasing healthy coping styles in women with MS. If these findings are replicated in future studies, widespread adoption of this program may help women with MS cope more successfully with their disease.