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Background: Psoriasis has important physical and psychosocial effects that extend beyond the skin. Understanding the impact of treatment on health‐related quality of life (HRQoL) and patient‐perceived symptom severity in psoriasis is key to clinical decision‐making. Objectives: This post hoc analysis of the PSO‐LONG trial data assessed the impact of long‐term proactive or reactive management with fixed‐dose combination calcipotriene 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) foam on patient‐reported outcomes (PROs) in patients with psoriasis vulgaris. Methods: Five hundred and twenty‐one patients from the Phase 3, randomized, double‐blind PSO‐LONG trial were included. An initial 4‐week, open‐label phase of fixed‐dose combination Cal/BD foam once daily (QD) was followed by a 52‐week maintenance phase, at the start of which patients were randomized to a proactive management arm (Cal/BD foam twice weekly) or reactive management arm (vehicle foam twice weekly). Patient‐perceived symptom severity and HRQoL were assessed using the Psoriasis Symptom Inventory (PSI), the Dermatology Life Quality Index (DLQI) and the EuroQol‐5D for psoriasis (EQ‐5D‐5L‐PSO). Results: Statistically and clinically significant improvements were observed across all PRO measures. The mean difference (standard deviation) from baseline to Week 4 was −8.97 (6.18) for PSI, −6.02 (5.46) for DLQI and 0.11 (0.15) for EQ‐5D‐5L‐PSO scores. During maintenance, patients receiving reactive management had significantly higher DLQI (15% [p = 0.007]) and PSI (15% [p = 0.0128]) and a numerically lower EQ‐5D‐5L‐PSO mean area under the curve score than patients receiving proactive management (1% [p = 0.0842]). Conclusions: Cal/BD foam significantly improved DLQI, EQ‐5D‐5L‐PSO and PSI scores during the open‐label and maintenance phases. Patients assigned to proactive management had significantly better DLQI and PSI scores and numerically better EQ‐5D‐5L‐PSO versus reactive management. Additionally, baseline flare was associated with worse PROs than the start of a relapse, and patients starting a relapse also had worse PROs than patients in remission. [ABSTRACT FROM AUTHOR]