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Background Multiple sclerosis (MS) notably affects adults of working age. For persons with MS (PwMS), being employed enhances their quality of life and it may be regarded as an indicator of overall functioning. Thus, ensuring work participation in PwMS is of general public health interest. Objective To examine relevant socio-demographic, MS-, health- and work-related factors, including psychosocial working conditions, associated with currently working PwMS in Switzerland and their expected work retention. Methods Using cross-sectional data of PwMS in the Swiss MS Registry (n = 541, median age = 48 [IQR 40;55]), multivariable logistic regression models were computed. First, currently working PwMS were characterised in comparison with those not currently working. Second, expected work retention, operationalized as subjective judgement “likely to work in the same job in 2 years”, was examined within the group of currently working PwMS. Results The factors age (OR 0.96, 95% CI 0.92–0.99), sex (OR 0.28, 95% CI 0.13–0.60), highest achieved job position (OR 1.21, 95% CI 1.01–1.46), health-related quality of life (HRQoL) (OR 1.02, 95% CI 1.01–1.04) and the number of MS symptoms (OR 0.90, 95% CI 0.82–0.98) were associated with currently working PwMS. Moreover, HRQoL (OR 1.07, 95% CI 1.04–1.10) and psychosocial working conditions, such as job resources (e.g. autonomy, control or social support) (OR 2.83, 95% CI 1.50–5.33) and job demands (e.g. workload, time pressure) (OR 0.41, 95% CI 0.18–0.90) were important factors for expected work retention among this group. Conclusions Resourceful psychosocial working conditions are crucial for PwMS to maintain employment. Employers could contribute to work retention among PwMS by creating a work environment with resourceful psychosocial working conditions and providing, for instance, social support.