In the Brazilian public healthcare system, natalizumab is recommended as fourth-line treatment for relapsing-remitting multiple sclerosis (RRMS). Although natalizumab has already demonstrated higher effectiveness compared with fingolimod in some studies, this real-world study was conducted to evaluate annualized hospitalization rates (AHR) in Brazil for both treatments when switching from platform therapies. As secondary goals, we analyzed RRMS treatment patterns and hospitalization profiles.We extracted data from the DATASUS database of patients with MS (ICD-10 G35) who initiated treatment from January 2012 to December 2017. Two cohorts were screened for different purposes. Cohort 1 was used to analyze treatment patterns and hospitalization profiles and was defined as individuals who had at least one claim related to MS therapies and had received at least two lines of treatment. The second cohort, which was a subset of the first, was used to compare natalizumab's and fingolimod's AHR reduction from previous treatment lines and included patients switching from platform therapy to one of these two drugs. Cohort 2 adjustment was assessed through two different statistical methods: propensity score (PS) and inverse probability weighting (IPW).Of 29,410 patients screened, 2,876 were included in cohort 1. Three quarters of hospitalizations reported in this cohort were for treatment of MS relapse. Cohort 2 included 1,005 patients, and natalizumab was more commonly used (n = 540) than fingolimod (n = 465). Both PS and IPW analyses showed that patients treated with natalizumab had a statistical significantly reduction in AHR compared with first-line treatment (p<0.01 for both PS and IPW), while fingolimod did not result in significant reduction in AHR (p = 0.20 for PS and p = 0.17 for IPW).This study provides real-world evidence of natalizumab's and fingolimod's effectiveness in terms of AHR, with an increased reduction in AHR with natalizumab. The findings of this study also provide information to support disease management and healthcare planning in the Brazilian public healthcare system.