OBJECTIVES: To evaluate the cost-effectiveness of infliximab, adalimumab, certolizumab pegol, and vedolizumab in Moderate-to-Severe Crohn’s disease from a US payer perspective with evidence synthesis from a Bayesian network meta-analysis (NMA). METHODS: A Markov model was constructed to evaluate the lifetime cost-effectiveness of biologics and active control (azathioprine) in Crohn’s disease. The model used a 3-month cycle with six health states: Moderate-to-Severe, Mild-to-Severe, Remission, Severe/Fulminant, Post-Surgery, and Death. Transition probabilities from Moderate-to-Severe to Remission were synthesized using a Bayesian NMA. Other transition probabilities and utility values were derived from the literature. Drug costs were based on Medicare Part-B Drug and Biological Average Sales Price Payment files. Costs and QALYs were discounted at 3-percent/year. One-way and probabilistic sensitivity analyses (PSA) tested the robustness of the results. Willingness-to-pay threshold of $100,000/QALY was considered cost-effective.  RESULTS: Transition probabilities (Moderate-to-Severe to Remission states) for active control, infliximab, adalimumab, certolizumab pegol, and vedolizumab were 0.240, 0.392, 0.483, 0.422, and 0.426, respectively. Utility gained for active control, infliximab, adalimumab, certolizumab pegol, and vedolizumab were 17.84, 26.32, 26.35, 26.33, and 26.33 QALYs, respectively. Total direct costs for active control, infliximab, adalimumab, certolizumab pegol and vedolizumab were $289,300, $330,700, $425,900, $547,800, and $423,200, respectively. ICER for infliximab compared to active control was $4,881/QALY gained. ICER for adalimumab compared to infliximab was $3.5 million/QALY. Certolizumab pegol and vedolizumab were eliminated by extended dominance. In comparison between infliximab and active control, the model was robust to all variables in one-way sensitivity analysis. Results comparing adalimumab and infliximab were sensitive to utility values. In the PSA, infliximab was 99.6% cost-effective compared to active control; however, adalimumab was only 2.6% cost-effective. CONCLUSIONS: Infliximab is cost-effective relative to active control, whereas, adalimumab is not when compared to infliximab. Other studies have reported varying results which highlights the importance for further work in this area.