OBJECTIVES: To evaluate the efficacy and safety of FDA-approved biologics for moderate-to-severe Crohn’s disease (CD). METHODS: We conducted a literature search using PubMed, EMBASE, and Cochrane library, and identified articles from inception to October 10, 2014. The combination of search terms included: “infliximab,” “adalimumab,” “certolizumab pegol,” “vedolizumab,” and “Crohn’s disease.” Studies were selected if they were randomized placebo-controlled trials >/= 50 weeks of follow-up; that evaluated one or more biologics of interest, provided results about clinical remission (defined as CD Activity Index<150 points), serious infections and/or serious adverse events; and was conducted in adults. The principal aim was to compare clinical remission at the end of the study period between biologics. Secondary aims included the probability of experiencing a serious infection or serious adverse event. Bayesian network meta-analyses were performed to synthesize results; and comparisons were summarized using odds ratios (OR) and 95% credible intervals (CrI). RESULTS: Among 324 articles identified, 11 met inclusion criteria. The odds of achieving clinical remission were greater with adalimumab than with vedolizumab (OR=1.33; 95%CrI: 0.67-2.42), infliximab (OR=1.40; 95%CrI: 0.86-2.53) and certolizumab pegol (OR=1.23; 95%CrI: 0.72-2.29); all not statistically significant. Similarly, the odds of clinical remission were greater with certolizumab pegol than with vedolizumab (OR=0.91; 95%CrI: 0.48-1.60) and infliximab (OR=1.18; 95%CrI: 0.68-1.92); all not statistically significant. Certolizumab pegol had the highest probability of serious infections (0.053%) followed by vedolizumab (0.022%), infliximab (0.010%), and adalimumab (0.008%). Vedolizumab had the highest probability of serious adverse events (19%) followed by certolizumab pegol (10%), infliximab (10%), and adalimumab (7%). CONCLUSIONS: We did not find any statistically significant differences between biologics in clinical remission, serious infections, and serious adverse events, which highlights the importance for comparative effectiveness research (CER) in this area. CER will be able to guide clinical and formulary decision-makers in selecting biologics with high value for CD.