Background: Social and environmental participation endeavors are theorized to shape one's general satisfaction with the overall employment situation facing people with MS. Objective: Responding to a national survey of the employment concerns of Americans with multiple sclerosis (MS), this study examined the extent to which factors at the demographic, disease-related, and social and environmental participation levels contribute to the predictability power for general satisfaction with the employment situation for people with MS. Method: Participants in this study consisted of 1,149 members of nine National Multiple Sclerosis Society (NMSS) chapters representing 21 states and Washington, DC. In a hierarchical multiple regression analysis, participants were mostly older (average age of 50 years) White (74%) individuals, nearly half of whom were unemployed (47%) but well educated (98% were high school graduates, 45% were college graduates). Findings: Findings underscore the complexity involved in predicting how satisfied people with MS are with their overall employment situation. Conclusions: Younger, less educated individuals with higher levels of perceived quality of life who were employed full-time and experiencing no or lower levels of cognitive impairment were more likely than other participants to be satisfied with 17 high-priority employment concerns.