The aim of this study was to compare marital satisfaction and mental health in male and female multiple sclerosis patients with healthy males and females. In a correlation study, 59 MS patients in Tehran (31 female and 28 male, with a range of 25 to 55 years old) were selected by the random cluster sampling method and 59 healthy individuals were matched with them in sex and age. Then both groups filled in the marital satisfaction questionnaire of Enrich and GHQ. The test of multi-variance analysis showed that, regardless of the gender, for people with MS disease, the marital satisfaction and the whole of its subscales except the religion and the mental health and its all sub-scales, are established at a significantly low level. However, the comparison of these groups due to the gender showed that in the satisfaction elements and personality issues, the relationship between marital and leisure time of women patients is worse than men; however, healthy women scores in financial management are lower than healthy men. In addition, in the elements of mental health, women and men patients are similar to each other but healthy women have higher physical symptoms than healthy men (P < .05). These results represent the necessity of applying approaches to increase the satisfaction of the marital and mental health of patients and training the couples for cooperation and higher perception.