OBJECTIVES: To evaluate the cost-effectiveness of adalimumab plus standard of care (ADA+SOC) vs. SOC alone in moderate-to-severe ulcerative colitis (UC) patients with an inadequate response to SOC and to assess the total cost differences comparing ADA+SOC to infliximab (IFX)+SOC and to golimumab (GOL)+SOC. METHODS: A Markov model was developed to simulate the progression of patients receiving ADA+SOC or SOC over a 5-year time horizon from the Canadian publicly-funded health system’s perspective, considering direct costs only in the base case. Transitional probabilities of pre-surgery and surgery-related states for ADA+SOC and SOC were derived from ADA trials and from literature. Health utility and cost inputs (medications, medical services, surgery, and surgery-related mortality) came mainly from literature. Additionally, a cost-minimization analysis (CMA) compared the total 5-year costs of biologics (ADA, IFX and GOL) assuming IFX and GOL having the same efficacy as ADA. Results were expressed in costs per quality-adjusted-life-years (QALY) gained for ADA+SOC vs. SOC alone and in total cost differences for ADA+SOC vs. IFX+SOC and vs. GOL+SOC. Deterministic and probabilistic sensitivity analyses (DSA, PSA) were performed. RESULTS: In the base case, the incremental costs per QALY gained for ADA+SOC vs. SOC were C$96,812 (in 2013 Canadian dollars [C$]). Results from DSA ranged from C$62,362 to C$109,461. PSA revealed that ADA+SOC was cost-effective in 58% and 81% of cases at C$100,000/QALY and C$120,000/QALY thresholds, respectively. The CMA predicted total cost savings of C$23,823 and C$4,279 comparing ADA+SOC to IFX+SOC and to GOL+SOC over 5 years. DSA and PSA results showed that ADA+SOC led to cost savings in all scenarios comparing to IFX+SOC and in all but one DSA-based and all PSA-based scenarios comparing to GOL+SOC. CONCLUSIONS: The ADA+SOC strategy appeared to provide reasonable cost-effectiveness value compared with SOC alone and significant cost-saving benefits compared to IFX+SOC and GOL+SOC.