Summary 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. What's already known about this topic? Etanercept and infliximab are both effective and safe treatments for psoriasis. No comparative long‐term data are available that are independent from pharmaceutical companies. What does this study add? The onset of action and physician‐reported efficacy for week 12 and 24 is significantly better for infliximab. There was less of a difference in efficacy for patient‐reported outcomes. Long‐term data show no significant differences, based on the duration of remission after stopping treatment and maintenance treatment until week 48. Respond to this article Linked Comment: Burden. Br J Dermatol 2017; 176:565.