BACKGROUND: Work productivity loss (WPL) is a major contributor to the indirect costs of psoriasis. Newer biologic therapies are effective at reducing disease symptoms and improving quality of life, but their impact on WPL and associated indirect cost savings compared to previously approved biologic therapies is largely unknown. OBJECTIVES: To compare the effects of guselkumab and adalimumab on WPL and associated indirect cost savings in patients with moderate-to-severe psoriasis. METHODS: Using data from the VOYAGE 1 (NCT02207231) trial, improvements from baseline in Dermatology Life Quality Index (DLQI) work/study domain scores were compared for patients receiving guselkumab or adalimumab at 24 and 48 weeks of treatment. Improvements in WPL and associated cost savings were calculated using a previously established DLQI-WPL algorithm. RESULTS: Among patients who could not work/study at baseline (DLQI work/study domain score = 3), a significantly greater proportion of guselkumab-treated patients could work/study without problems (DLQI work/study domain score = 0) than adalimumab-treated patients at Weeks 24 and 48. Improvements from baseline in WPL and associated cost savings were greater with guselkumab than with adalimumab at Week 48. CONCLUSIONS: Guselkumab was superior to adalimumab for improvement in WPL and associated indirect cost savings, and its use may reduce the economic burden of psoriasis.