This study explores how employment is associated with perceived physical and mental health status in people with multiple sclerosis (MS) adjusted for sociodemographic and clinical variables stratified by age. The sample consisted of 184 MS patients divided into a younger (less than 45 years) and an older (greater than or equal to 45 years) age group. Respondents underwent an interview, a neurological examination on disability [Expanded Disability Status Scale (EDSS)], and completed the Short Form-36 Health Survey. Of the respondents (mean age 40.5 plus or minus 6.2 years), 43.5% were employed. Significant differences between younger and older patients were found in employment, EDSS, disease duration, and five Short Form-36 Health Survey dimensions. Block-step multiple regression explained 32.4% of the variance in physical health and 14.5% in mental health in the younger group. Being employed was significantly related to good physical health, whereas EDSS diminished the effect of being employed on physical health. The most important variable for mental health was employment status in the younger group. For the older age group, 19.1% of the variance in physical health and 14.0% of the variance in mental health was explained by the studied variables. Male gender and a lower EDSS were significant explanatory variables of better physical health. Male gender significantly explained mental health in the older age group. In conclusion, employment status was an explanatory variable for physical health and mental health in the younger patients. EDSS played a significant role in physical health for all patients. A vocational rehabilitation program could prevent eventual nonemployment and improve health outcomes in older MS people.