Summary: Background: Patients with plaque psoriasis treated with biologic therapies need more efficacious, safe and convenient treatments to improve quality of life. Risankizumab and secukinumab inhibit interleukin‐23 and interleukin‐17A, respectively, and are effective in adult patients with moderate‐to‐severe plaque psoriasis but have different dosing regimens. Objectives: To compare directly the efficacy and safety of risankizumab vs. secukinumab over 52 weeks. Methods: IMMerge was an international, phase III, multicentre, open‐label, efficacy–assessor‐blinded, active‐comparator study, in which adult patients with chronic, moderate‐to‐severe plaque psoriasis were randomized in a 1 : 1 ratio to treatment with risankizumab 150 mg or secukinumab 300 mg. Primary efficacy endpoints were the proportions of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at week 16 (noninferiority comparison with margin of 12%) and week 52 (superiority comparison). Results: In total 327 patients from nine countries were treated with risankizumab (n = 164) or secukinumab (n = 163). Risankizumab was noninferior to secukinumab in the proportion of patients achieving PASI 90 at week 16 [73·8% vs. 65·6%; difference of 8·2%, 96·25% confidence interval (CI)−2·2 to 18·6; within the 12% noninferiority margin] and superior to secukinumab at week 52 (86·6% vs. 57·1%; difference of 29·8%, 95% CI 20·8–38·8; P < 0·001), thus meeting both primary endpoints. All secondary endpoints (PASI 100, static Physician's Global Assessment 0 or 1, and PASI 75) at week 52 demonstrated superiority for risankizumab vs. secukinumab (P < 0·001). No new safety concerns were identified. Conclusions: At week 52, risankizumab demonstrated superior efficacy and similar safety with less frequent dosing compared with secukinumab. What is already known about this topic? The need remains for treatments with sustained efficacy and a more convenient dosing schedule in moderate‐to‐severe psoriasis.Risankizumab and secukinumab are indicated for the treatment of adults with moderate‐to‐severe plaque psoriasis and target interleukin‐23 and interleukin‐17, respectively.To date, risankizumab and secukinumab have not been directly compared. What does this study add? IMMerge directly compared the safety and efficacy of risankizumab and secukinumab in patients with moderate‐to‐severe plaque psoriasis using ≥ 90% improvement in Psoriasis Area and Severity Index at weeks 16 (noninferiority) and 52 (superiority) as primary endpoints.In terms of efficacy risankizumab was noninferior to secukinumab at week 16 and superior to secukinumab at week 52 of treatment based on primary endpoint analyses. The two medications had a similar safety profile. Linked Comment:Schmitt-Egenolf. Br J Dermatol 2021; 184: 3–4. Plain language summary available online [ABSTRACT FROM AUTHOR]