Summary Background It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. Objectives To assess the number of treatment episodes (TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. Methods Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni‐ and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. Results In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24. Conclusions A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response. What's already known about this topic? A high clinical response in patients with psoriasis is shifting towards a 90% improvement compared with baseline Psoriasis Area and Severity Index (PASI 90). To date, no studies have assessed which patients with psoriasis are more likely to achieve a high clinical response at week 24 of biological treatment. What does this study add? We focused on high responders, defined as achieving PASI 100, PASI 90 or PASI ≤ 5. Frequency of reaching high clinical responses at 24 weeks of biological treatment was assessed, as were predictors that could identify patients with the ability to respond well to biological treatment. In only a limited number of treatment episodes are PASI 90 (15%) or PASI 100 (3%) achieved. Lower baseline body mass index is a predictor for achieving PASI ≤ 5. Linked Comment: Zheng. Br J Dermatol 2017; 176:576.