The etiology of multiple sclerosis (MS) is still not well known. Previous data show conflicting results regarding the association between MS and prior brain trauma. This study aims to investigate the risk for MS following a traumatic brain injury (TBI) using a large-scale cohort study design. This study used data from the National Health Insurance Research Database. A total of 72,765 patients with TBI were identified and included as the study cohort, and 218,295 randomly selected subjects were matched with the study cohort by sex and age as controls. We traced each patient individually for a 6-year period from their index health care utilization to identify those who received a subsequent diagnosis of MS. We used the Kaplan-Meier method and the log-rank test to compare the difference in 6-year MS-free survival rates between the two groups. Stratified Cox proportional hazard regressions were computed to compare the risk of developing MS for these two cohorts. Patients with TBI had a higher incidence of MS during the 6-year period than the comparison group (0.055% versus 0.037%). After excluding cases who died from non-MS causes, stratifying for hospitalization of cases as a proxy for severity, and adjusting for monthly income and geographic region of the community in which the patient resided, the hazard ratio (HR) of MS for patients with hospital-treated TBI injuries was 1.97 (95% CI 1.31,2.93, p<0.01) that of patients without TBI during the 6-year follow-up period after index health care use. Our study concludes that patients with TBI are at higher risk for subsequent MS over a 6-year follow-up period.