Background: Previous studies have shown an effect of tonsillectomy and greater risk for future autoimmune diseases. Currently there are only few outdated analyses of tonsillectomy and multiple sclerosis (MS) risk. Objective: To investigate the prevalence of tonsillectomy in MS patients and healthy controls (HCs). Methods: A total of 1000 subjects (779 MS patients and 221 HCs) completed a structured study questionnaire regarding MS diagnosis, age of onset, history of tonsillectomy, and age of tonsillectomy. In a subgroup of patients with available electronic medical records, Expanded Disability Status Scale (EDSS) scores at the time of recruitment and 5-years later were collected. Statistical analyses were performed with ? 2 test, odds ratio (OR), Student's t-test, Mann-Whitney U test, and ordinal regression.. Results: The MS population had a greater percentage of patients with history of tonsillectomy when compared to HCs [39.5% vs. 31.7%, OR 1.411 (CI 1.027-1.938), p = 0.034], driven by participants aged 50 or older [45.7% vs. 36.1%, OR 1.495 (CI 1.037-2.155) p = 0.031]. There was no difference of the age at tonsillectomy (median 8.0 vs. 6.5 years old, p = 0.26). However, the RRMS patients had their tonsillectomy procedure performed significantly later when compared to HCs (median 6.5 vs. 9.0 years old, p = 0.049). In an analysis of RRMS patients with available longitudinal data (n = 459), patients with a history of tonsillectomy were significantly older and had a longer disease duration (p < 0.001 and p = 0.025). After adjusting for the demographic differences, no history of tonsillectomy remained significant predictor of lower EDSS score categories both at the first (estimate =-0.467, Wald = 6.68, 95% CI-0.82 to-0.11, p = 0.01) and second timepoint (estimate =- 0.376, Wald = 4.4, 95% CI-0.73 to-0.02 p = 0.037). Conclusion: When compared to HCs, a greater percentage of MS patients underwent tonsillectomy. The role of tonsils, its relationship with early infection rates and/or antibiotic use in MS should be further investigated.