Background: There are currently no independent data available comparing infliximab and etanercept for the treatment of psoriasis. Objectives: To compare these biologics without funding from pharmaceutical companies. Methods: Overall, 50 patients were randomized to etanercept (n = 23) 50 mg subcutaneously twice weekly or infliximab (n = 25) 5 mg kg−1 intravenously at week 0, 2, 6, 14 and 22. After 24 weeks, 19 patients stopped and 22 continued treatment and were followed up to week 48. The primary outcome was ≥ 75% improvement of Psoriasis Area and Severity Index (PASI 75) at week 24. The secondary outcomes included PASI 75 at week 6 (onset of action) and week 12, Investigator's Global Assessment (IGA), Patient Global Assessment, impact on quality of life (Skindex-17 and SF-36), Treatment Satisfaction Questionnaire of Medication, duration of remission, maintenance treatment and safety. Results: At week 24, PASI 75 was achieved in 72% (infliximab) vs. 35% (etanercept) (P = 0·01). The onset of action was achieved in 52% (infliximab) and 4% (etanercept). At week 12, 76% (infliximab) and 22% (etanercept) achieved PASI 75 (P < 0·001). At week 24, IGA ‘clear or almost clear’ was observed in 76% (infliximab) and 30% (etanercept) (P = 0·01). Skindex-17 symptom score was significantly better for infliximab. Maintenance treatment achieved PASI 75 for 67% (n = 6) infliximab vs. 50% (n = 5) etanercept, at week 48 (P = 0·65). Mild adverse events were reported in 76% (infliximab) vs. 66% (etanercept). Conclusions: Infliximab showed a rapid and significant higher level of efficacy until week 24 compared with etanercept. Long-term data showed no significant differences between both groups at week 48. Safety parameters were comparable.