Objective: It is the objective of this study to estimate the cost per treatment success over a one-year timeframe of the five biologic therapies used to treat patients with moderate to severe psoriasis in the U.S. Methods: A Markov model was developed to compare the relative cost components in psoriasis treatment with biologics. Drug costs were based on wholesale acquisition cost with consideration of net contractual discounts and patient co-share or co-payment. Clinical efficacy, for both short-term (12 weeks) and longer-term (24+ weeks) treatment, was based on the published peer-reviewed literature. The primary economic endpoint was the cost of therapy (defined as the cost of drugs, laboratory, infusion, and professional services) per 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75) achieved. Analysis was conducted for each of the biologic agents currently utilized in the U.S. for this indication (adalimumab, alefacept, efalizumab, etanercept and infliximab). Model results were displayed for a time horizon of one year based on a switch to an appropriate alternate biologic agent in the event of suboptimal clinical response. Multiple one-way sensitivity analyses were conducted. Results: Across all the biologics evaluated there are significant differences in PASI 75 response at 12 weeks versus longer term (ranging from 59% to 20% across the agents at the end of one quarter of treatment and at the end of four quarters of treatment, respectively). The cost per PASI 75 was observed to be $26,460, $31,191, $28,217, $30,544 and $30,983 for therapy initiated with adalimumab, alefacept, efalizumab, etanercept and infliximab, respectively. Conclusion: While there are significant differences in the cost of the studied biologic agents initially, the CE results tend to converge over the first year of treatment. Further research needs to be conducted to evaluate the CE of treatment beyond a one-year period.