SummaryBackground Significant advances have been made in the treatment of moderate-tosevere plaque psoriasis with biological therapies; however, these agents may not work equally in all populations. Objectives To evaluate the efficacy of guselkumab in patient subgroups with moderate-to-severe psoriasis from the pooled guselkumab VOYAGE 1 and VOYAGE 2 phase III studies. Methods Using data from the pooled VOYAGE 1 and VOYAGE 2 psoriasis studies, analyses were performed to evaluate the consistency of efficacy [Investigator's Global Assessment (IGA) 0/1 (cleared or minimal psoriasis) and IGA 0 (cleared)] across subpopulations defined by demographics, baseline disease characteristics and previous psoriasis treatment. Results A total of 1829 patients were randomized. Baseline demographics, disease characteristics and previous psoriasis treatment were comparable across treatment groups in the pooled population. Guselkumab, an anti-interleukin (IL)-23 monoclonal antibody that binds to the p19 subunit of IL-23, provided substantial benefit across almost all subpopulations, with greater proportions of patients achieving IGA 0/1 vs. placebo at week 16, and vs. adalimumab (an antitumour necrosis factor monoclonal antibody) at week 24. Patients treated with guselkumab achieved greater efficacy (IGA 0/1 and IGA 0) compared with adalimumab at week 24 across all weight quartiles, most notably among patients weighing ≥ 100 kg. Conclusions This analysis demonstrates a high degree of efficacy with guselkumab treatment compared with placebo at week 16 and with adalimumab at week 24 among broad subpopulations of patients with varying baseline demographics, disease characteristics and previous psoriasis treatments.