Mild psoriasis may be burdensome; if symptoms are inadequately controlled, switching therapy may be warranted. In the Phase 3 NAVIGATE trial, patients with moderate-to-severe plaque psoriasis received ustekinumab for 16 weeks. Patients with inadequate response (Investigator's Global Assessment [IGA] ≥ 2) were randomized to switch to guselkumab or continue ustekinumab. This post-hoc analysis evaluated the patient subgroup with residual mild psoriasis (IGA = 2) after initial ustekinumab therapy. Outcomes assessed included the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Psoriasis Symptoms and Signs Diary (PSSD). Initially, 871 patients received ustekinumab. At Week 16, 161 randomized patients had residual mild psoriasis (IGA = 2). Among guselkumab- vs ustekinumab-treated patients at Week 28, 59.0% vs 27.7% achieved PASI 90, and 50.0% vs 21.0% achieved DLQI 0/1. Mean changes from baseline in PSSD score were -44 vs -28 and -50 vs -32, respectively, with thresholds of -40 considered clinically meaningful. Mean changes in PSSD itch score were -4.6 vs -2.9, with reductions ≥ 4.0 considered clinically meaningful. Treatment differences were maintained/increased through Week 52. Among patients with residual mild psoriasis after 16 weeks of ustekinumab, those switching to guselkumab had greater improvements in skin clearance, health-related quality of life, and patient-reported symptoms and signs than those continuing ustekinumab.