In France, few data sources are available to estimate the impact of multiple sclerosis (MS) on job retention and its consequences on the level of resources, especially in large representative samples. The aim of the present study was to measure impact of MS on employment rates, wages and income (including unemployment benefit, sickness benefit and disability pension) by comparing work trajectories of people living with MS with those of a matched control group. We used the HYGIE database, which is the result of the linkage of two administrative databases in the private sector for a random sample of over 900,000 people. In order to identify the causal effect of MS on employment after 1 to 20 years, the difference-in-differences method with matching (age, sex, career and health history) was used, overall and in subgroups. The year of entry in long-term disease status for MS was used to approximate the onset of MS. Overall, 946 people with MS were included. Their situation was fairly favorable before MS (88.1% in employment, resources higher than the median for the general population), but MS had strong and continuous negative effects. Indeed, at 10 years, the employment rate fell by 28.6 percentage points (pp) and the disability pension allowance increased by 50.5 pp; the wage percentile fell by 19.2 pp and the replacement income accounted for a growing share of total income (+ 39.7 pp). Although administrative data had several strengths, clinical information on the severity of the disease or on its therapeutic management was not available. In conclusion, this study shows that the effects of MS on the employed population in the private sector occur early in the disease course and are cumulative, and that replacement income helps to reduce the loss of resources thanks to the French health and social system.