OBJECTIVES: To evaluate the cost-effectiveness of biologic treatments for moderate to severe psoriasis in the UK. METHODS: A decision model similar to those utilized in NICE appraisals TA103, TA134, TA146, and TA180 was constructed consisting of 2 distinct periods, the trial and treatment periods. Clinical efficacy was estimated during the trial period based on the relative probabilities of achieving Psoriasis Area and Severity Index (PASI) response (50/75/90) obtained via a network meta-analysis of 15 randomized controlled trials of adalimumab, etanercept, infliximab, and ustekinumab. Weight-based dosing was calculated for infliximab and ustekinumab to reflect licensed use. Only patients who achieved PASI 75 response in the trial period continued into the treatment period. Treatment benefits were determined by the relationship between predicted PASI response and the EQ-5D health utility measure. Costs (2011 British pounds) were assessed from a UK National Health Services perspective and included drug acquisition, administration, monitoring and hospitalization costs. Drug acquisition cost for ustekinumab reflected the manufacturers’ UK Patient Access Scheme. Incremental cost-effectiveness ratios (ICERs) were calculated and treatments were ranked relative to supportive care. One-way sensitivity analyses, using alternative plausible values for key parameters, explored uncertainty in the results. RESULTS: Infliximab provided the most additional quality-adjusted life-years (QALYs) vs. supportive care (0.186) followed by ustekinumab (0.174) and adalimumab (0.169). In the base case, adalimumab was the most cost-effective biologic (£19,082/QALY vs. supportive care), followed by ustekinumab (£20,964/QALY), etanercept 25 mg BIW (£26,580/QALY), etanercept 50 mg BIW during the trial period followed by 25mg BIW (£28,719 per QALY), and infliximab (£46,844 per QALY). ICERs for ustekinumab and infliximab compared with adalimumab were £87,625 and £332,015, respectively. Adalimumab remained the most cost-effective in the majority of the sensitivity analyses. CONCLUSIONS: In this decision-model analysis, adalimumab was the most cost-effective biologic treatment for moderate to severe psoriasis in the UK.