BACKGROUND: Psoriasis is an immune-mediated inflammatory disease for which treatment has evolved over the past few years due to the introduction of immunobiologic and small molecule inhibitor medications. A better understanding of the comparative efficacies of drugs may help doctors to choose the most appropriate treatment for patients. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis to assess the efficacy of immunobiologic and small molecule inhibitor drugs for patients with moderate to severe psoriasis. DATA SOURCES: The EMBASE, PUBMED, LILACS, Web of Science and ClinicalTrials.org databases were searched for trials published to 21 July 2016. STUDY SELECTION: Only randomized, double-blind, placebo-controlled clinical trials that evaluated the efficacy of immunobiologics or small molecule inhibitors for moderate to severe plaque-type psoriasis were selected by two independent authors. No restrictions were used. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted the data and a random-effects model meta-analysis was performed. MAIN OUTCOMES AND MEASURES: The Psoriasis Area and Severity Index (PASI) 75 was considered the primary outcome, measured at the primary endpoint of each study. RESULTS: Thirty-eight studies were included in our analysis. The overall pooled effect favored biologics and small molecule inhibitors over placebo (risk difference [RD] 0.59, 95% confidence interval [CI] 0.58-0.60). Ixekizumab at a dose of 160 mg on week 0 and then every 2 weeks (RD 0.84, 95% CI 0.81-0.88), brodalumab 210 mg (RD 0.79, 95% CI 0.76-0.82), infliximab 5 mg/kg (RD 0.76, 95% CI 0.73-0.79), and secukinumab 300 mg (RD 0.76, 95% CI 0.71-0.81) showed a greater chance of response (PASI 75) when compared with placebo. LIMITATIONS: The methodology of a traditional meta-analysis does not allow for drugs to be ranked. Included studies used short-term endpoints (10-16 weeks) to evaluate the primary outcome, therefore long-term efficacy could not be determined. CONCLUSIONS AND RELEVANCE: The anti-IL-17 drugs brodalumab, ixekizumab and secukinumab showed an equal or greater chance of helping patients achieve a 75% improvement on PASI compared with other reviewed drugs.