OBJECTIVES: Etanercept, infliximab, ustekinumab, and adalimumab have been granted marketing authorization for the treatment of moderate-to-severe psoriasis in Germany.  The objective of this study is to evaluate cost-effectiveness of biologic treatments from the German Social Health Insurance (SHI) perspective.  METHODS: A simple decision model was constructed to assess the cost-effectiveness of biologics compared to supportive care for the treatment of moderate-to-severe psoriasis over a one-year time horizon.  Clinical efficacy was based on the relative probabilities of achieving PASI75, and PASI 90 response obtained via a network meta-analysis.  Weight-based dosing was assumed for infliximab and ustekinumab.  Costs were assessed in terms of 2012 euros, and included drug acquisition, administration, laboratory tests, clinic visits, and hospitalization costs. Cost-effectiveness from payer perspective was assessed as the cost-per-PASI75 response and cost-per-PASI90 response compared with supportive care (no systemic therapy) over a one-year time horizon.  One-way sensitivity analyses, where key parameters were changed to alternative plausible values, explored uncertainty in the results. RESULTS: In the base case, adalimumab was found to be the most cost-effective compared to supportive care (€25,378 per PASI75 responder and €46,870 per PASI90 responder), followed by infliximab (€30,719 per PASI75 responder and €47,300 per PASI90 responder), ustekinumab (€31,953 per PASI75 responder, and €57,852 per PASI90 responder), etanercept 50mg BIW (€43,049 per PASI75 responder and €101,306 per PASI90 responder), and etanercept 25 mg BIW (€43,156 per PASI75 responder and €111,369 per PASI90 responder).  The incremental cost per PASI 75 responder gained and the incremental cost per PASI 90 for infliximab compared to adalimumab were €51,812 and €48,112, and €87,942 and €106,911 respectively for ustekinumab. Adalimumab remained the most cost-effective over the vast majority of the one-way sensitivity analyses.  CONCLUSIONS: This study found that adalimumab is the most cost-effective biologic treatment for moderate to severe psoriasis from the German SHI perspective.