Illness severity and sociodemographic characteristics of 7,053 employees with multiple sclerosis and 11,043 peers not in the workforce were compared (Hedges’ g with 95% confidence interval and p values). Pooled findings from 25 studies confirmed the main role of a relapsing–remitting disease course and higher education to employment. To a lesser extent, disease duration, fatigue and pain symptoms and age also differentiated the two groups. Vocational interventions for persons with multiple sclerosis should focus on job retention, including mechanisms to accommodate and facilitate functional independence. Longitudinal data are needed to distinguish the characteristics of those who achieve and maintain competitive employment.