Objective: Five biological treatments are registered for psoriasis, the tumor necrosis alpha (TNF-alpha) inhibitor adalimumab, etanercept and infliximab and the T-cell modulator alefacept, efalizumab. Our objectives were to analyse the efficacy of registered biological drugs in psoriasis and also to compare their efficacy on a pharmacological group level. Methods: Cochrane Highly Sensitive Search Strategy was used to identify RCTs in MEDLINE. Inclusion criteria were: a) treatment of psoriasis b) outcome data on the proportions of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI) from baseline. The quality of selected studies was measured using the Jadad-score. Data were entered into Review Manager 4.2 software. The chosen summary statistic variable was the number needed to treat (NNT). Due to lack of face-to-face evidence on biologics, an indirect comparison of the trials was conducted, applying the method proposed by Butcher. Results: Sixteen RCTs involving 7339 patients were identified. The active treatment was adalimumab in 1 trial (n=147), alefacept in three trials (n=1289), efalizumab in four trials (n=2444), etanercept in four trials (n=1964) and infliximab in four trials (n=1495). All trials were placebo controlled and the primary follow-up time was 12 weeks. The primary outcome was PASI75 criteria in all trials. To achieve PASI75, the number of patients needed to treat (95% confidence intervals) with adalimumab 40 mg/eow, alefacept 15 mg, efalizumab 1 mg/kg, etanercept 2 x 50 mg/week and infliximab 5 mg/kg were 2.04 (1.54-2.94), 5.00 (3.57-7.69), 3.85 (3.13-5.26), 2.27 (2.08-2.50) and 1.32 (1.25-1.39), respectively. Indirect comparisons of TNF-alpha inhibitors and T-cell modulators yielded the odds ratios of 5.54 (3.65-8.42). Conclusion: All biologicals were superior to placebo, alefacept with the highest and infliximab with the lowest NNT. TNF-alpha inhibitors were significantly superior to T-cell modulators.