Work difficulties are a primary issue of multiple sclerosis (MS). This is because disease onset usually occurs during a time when establishing a career and employment is of paramount importance. The MSWDQ-23 (Multiple Sclerosis Work Difficulties Questionnaire) was developed to assess work difficulties in MS. The WORKSEP project aimed to adapt and validate the French MSWDQ-23 and develop cutoff scores through a multicentric study in 14 centers across France. Two hundred and six persons with MS were recruited: 149 with relapsing-remitting MS and 57 with progressive forms of MS. They completed the MSWDQ-23 in French, the DEX to assess the subjective cognitive executive complaint, and the SF-36 evaluating mental (MC) and physical (PC) health-related quality of life. The results indicated that the French version of MSWDQ-23 has high internal consistency (Cronbach's α: 0.93) and test-retest reliability (ICC=0.83). A confirmatory factor analysis demonstrated a scale structure identical to the original English version comprising physical barriers (PB), psychological and cognitive barriers (PCB), and external barriers (EB). The construct and convergent validity were strong. A higher level of work difficulties at PB score was related to a higher level of disability at the EDSS and lower PC quality of life, and a higher level of PCB was related to higher cognitive executive complaints and lower MC quality of life. ROC curves based on the difference between employed and unemployed patients allowed for determining cutoff values of 32 for the total score, 37 for PB, and 27 for PCB. This study allowed the validation of the MSWDQ-23 in the French language and is the first to propose a cutoff. Determining the cutoff value enables identifying patients needing intervention and targets the limitations that MS patients may encounter in the workplace. This easy-to-use instrument provides the opportunity to propose an adapted rehabilitation program or work adjustments to improve the quality of life in patients with MS.