Objectives: To compare the liver safety profile of interferon β (IFN β) and teriflunomide in patients with multiple sclerosis. Methods: A network meta-analysis was carried out following the Cochrane Collaboration methodology. All trials comparing all types of IFN β with teriflunomide, or disease-modifying drugs, or placebo in RRMS were included. An indirect comparison network meta-analysis within a Bayesian framework with STATA (version 13.0) was done for this study. Results: The database searches yielded 284 titles, with 15 records as duplicates. One study was identified by manually searching. Thirteen articles were included in the systematic review. Twelve studies compared IFN β (4203 patients) vs another DMT. Four studies evaluated the effectiveness and safety of teriflunomide (906 patients) vs another DMT. Six studies reported drug-induced liver injury as per the Hy's Law. However, only one study had a direct comparison and reported no cases of liver toxicity in either group, so it was not possible to estimate the OR. The indirect comparisons metanalysis shows that there was no statistically-significant difference between teriflunomide and IFN β (OR 1.09, 95% CI 0.02–2.16). Conclusions: There were no significant difference when comparing IFN β and teriflunomide in terms of liver failure or elevation of transaminases.