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Vaccination is a key strategy for controlling the SARS-CoV-2 pandemic. Acceptance of SARS-CoV-2 vaccines by chronically ill patients, such as multiple sclerosis (MS) patients, plays an important role in prevention of complicated disease course. This longitudinal, prospective, multi-centre-study of German MS-patients aimed to detect socio-demographic, clinical, or psychological determinants of attitudes towards standard vaccines, SARS-CoV-2 vaccines, and governmental measures before/during the pandemic. Exactly 404 MS-patients were investigated by standardized questionnaires and structured interviews on socio-demographic, clinical-neurological, and psychological characteristics, vaccination status, and vaccination from June 2019. Data on SARS-CoV-2 vaccination willingness were collected in two follow-up assessments (1st: June to July 2020, before SARS-CoV-2 vaccine availability, N = 200; 2nd: March to May 2021, after SARS-CoV-2 vaccine availability, N = 157). Age, sex, MS course type, depression, and personality characteristics (Extraversion, Novelty seeking, Self-directedness, and Cooperativeness) were significantly associated with vaccination willingness. Although the majority of MS-patients showed SARS-CoV-2 vaccination willingness at both follow-ups (1st: 60%, 2nd: 61%), a substantial proportion had concerns and were undecided or opposed to vaccination. Socio-demographic variables like age and sex, psychopathological status, and various personality characteristics might influence vaccination willingness and should be considered when discussing with MS-patients about SARS-CoV-2 vaccination., (© 2022. The Author(s).)