OBJECTIVES Teriflunomide and dimethyl fumarate (DMF), oral therapies for relapsing–remitting multiple sclerosis (RRMS), have demonstrated efficacy in clinical trials. Despite challenges in comparing outcomes across studies, exploratory analyses of treatment effects can be compared informally using relative reductions in a specific endpoint. However, these outcomes do not account for differences in disease severity among study populations or differences on very low event rates. The number needed to treat (NNT) to prevent an event is an important outcome to consider for any comparisons within the field of MS. METHODS NNTs were derived using data from studies with teriflunomide 14 mg (TEMSO, NCT00134563; TOWER, NCT00751881) or DMF (DEFINE, NCT00420212; CONFIRM, NCT00451451) based on inverse of absolute differences between treatment and placebo groups. RESULTS Teriflunomide studies included patients with progressive disease; patients in DEFINE had slightly lower Expanded Disability Status Scale scores. Teriflunomide and DMF significantly reduced risk of relapse (all studies). NNTs to prevent one relapse were similar across studies (5.9 [TEMSO], 5.6 [TOWER], 5.3 [DEFINE], 5.6 [CONFIRM]). Risk of disability progression sustained for 12 weeks was significantly reduced in TEMSO, TOWER, and DEFINE but not CONFIRM. Corresponding NNTs to prevent disability progression were 13.8, 17.4, 10.8, and 30.2. Risk of relapse leading to hospitalization was significantly reduced in TEMSO and TOWER but not in DEFINE and CONFIRM. Corresponding NNTs were lower in TEMSO (12.5) and TOWER (20) than in DEFINE (50) and CONFIRM (50). CONCLUSIONS Using the NNT approach, we demonstrate a comparable effect size for teriflunomide and DMF on relapse. NNTs to prevent disability progression with teriflunomide showed a consistent significant reduction in risk versus placebo in both TEMSO and TOWER, whereas for DMF, comparable NNTs were observed only in DEFINE, and not in CONFIRM. Reduction of risk for relapse leading to hospitalization was significant only for teriflunomide.