OBJECTIVES To evaluate cost-effectiveness of infliximab and adalimumab for patients with refractory moderate-to-severe active ulcerative colitis (UC) in Canada. METHODS A four-health state Markov model was constructed to compare cost-effectiveness of three management strategies: A) usual care without anti-tumor necrosis factor á (anti-TNF-á); B) 5 mg/kg infliximab for responders and adalimumab for nonresponders; and C) 5 mg/kg infliximab for responders, 10 mg/kg infliximab for those lost their response in the maintenance stage, and adalimumab for nonresponders to the initial therapy. ACT1 and ACT2 randomized clinical trials were two main sources of clinical parameters. The primary outcome measure was the incremental cost-effectiveness ratio (ICER) between the strategies. Both deterministic and probabilistic sensitivity analyses were performed. RESULTS In the base case analysis, The ICER was $381,133/QALY for the strategy B versus the strategy A and $609,390/QALY for the strategy C versus the strategy A. The strategy C was dominated by the strategy B. The ICERs were sensitive to the remission rates, early surgery rate, and utility values. When the willingness to pay (WTP) was less than $150,000/QALY, the probability of the strategy A being the optimal strategy was 1.0. The probability of strategy B being optimal was 0.5 when the WTP increased to $400,000/QALY. The probability of the strategy C being the optimal strategy was very low despite the wide range of WTP values. CONCLUSIONS Although infliximab and adalimumab demonstrated clinical benefits over standard treatment in patients with refractory UC, the cost-effectiveness of these treatments are not attractive due to significantly higher costs in Canada.