IMPORTANCE: Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti-tumor necrosis factor (TNF) treatment of psoriasis. OBJECTIVE: To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis. DESIGN: Retrospective series of patients with psoriasis who received anti-TNF therapy (infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks. SETTING: Two psoriasis referral centers. PARTICIPANTS: Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents. INTERVENTION: Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping. MAIN OUTCOMES AND MEASURES: The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes. RESULTS: Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity allelesmay contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF. CONCLUSIONS AND RELEVANCE: Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.