Summary Background The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long‐term effectiveness of biologics in daily‐practice psoriasis treatment is currently lacking. Objectives To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily‐practice psoriasis treatment and to correct for confounders. Methods Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. Results We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). Conclusions Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab. What's already known about this topic? Randomized controlled clinical trials (RCTs) have shown that biologics are effective in treating selected patients with psoriasis. RCTs comparing ustekinumab with adalimumab or etanercept with adalimumab have not been performed. Patients from RCTs differ from patients in daily practice, and this might influence the effectiveness of biologics in the clinic. What does this study add? This prospective daily‐practice study compared the 1‐ and 5‐year effectiveness of adalimumab, etanercept and ustekinumab in psoriasis, corrected for confounders. We showed a significantly higher confounder‐corrected Psoriasis Area and Severity Index (PASI) decrease for ustekinumab vs. etanercept over 5 years. At 1 year of treatment, patients treated with adalimumab and ustekinumab had a higher chance of attaining PASI 75 than patients on etanercept after correction for confounders. Etanercept was the agent most often prescribed in high doses in daily practice. Respond to this article Linked Comment: Ormerod. Br J Dermatol 2017; 176:856–857