OBJECTIVES: To determine the cost-effectiveness of ustekinumab versus etanercept among Canadian adults with severe plaque psoriasis who have an inadequate response, are intolerant or contraindicated to at least one conventional systemic therapy. METHODS: The York Model, developed to evaluate biologics for the National Institute for Health and Clinical Excellence, was adapted to the Canadian environment.  The model consisted of an initial 12-week trial period based on results from ACCEPT, an active-control phase III trial which demonstrated superior efficacy of ustekinumab versus etanercept. The maintenance period, consisted of the trial results extrapolated over a 10-year time horizon. The cost-utility analysis compared estimates of expected costs and health effects of ustekinumab 45mg q12w and etanercept 50mg biw for 12 weeks and qw thereafter.  Response was defined as achievement of ≥ PASI 75 from the ACCEPT trial. Non-responders were switched to supportive care. Resource utilization was obtained from the literature and a Delphi panel of Canadian dermatologists.  Direct healthcare costs were obtained from the literature and expert opinion. Utility was mapped from DLQI to EQ-5D using the algorithm used by the York Model. Costs and outcomes were discounted at 5%.   RESULTS: Mean annual costs and QALYs for ustekinumab were $16,835 and 0.1464 compared to $19,558 and 0.1419 for etanercept. These results were robust to changes in parameter estimates. Not knowing the costs of adverse events over the 10-year time horizon was a limitation of the analysis. Cost-effectiveness acceptability curves show that at all levels of willingness- to-pay for one additional unit of efficacy, ustekinumab 45mg remains a more cost-effective treatment option than etanercept. CONCLUSIONS: Ustekinumab was more effective and less costly than etanercept over a 10-year time horizon, suggesting that ustekinumab is a dominant treatment option relative to etanercept for the treatment of patients with severe plaque psoriasis.