INTRODUCTION: Mirikizumab demonstrated significant efficacy compared with placebo in patients with Crohn's disease (CD) in the phase 3 VIVID-1 study. In this study, we report the impact of mirikizumab vs placebo on health-related quality of life (HRQoL) and work productivity in VIVID-1. METHODS: VIVID-1 patients randomized to receive mirikizumab (N = 579), or placebo (N = 199) were included. The effect of mirikizumab on HRQoL was assessed at weeks 12 and 52 using the Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form-36 Health Survey (SF-36), EQ-5D-5L visual analog scale, and Work Productivity and Activity Impairment: CD measures. The Cochran-Mantel-Haenszel test with nonresponder imputation (binary end points) and analysis of covariance with modified baseline observation carried forward (continuous end points) were used for treatment comparisons. RESULTS: Greater improvements in the mean change from baseline to weeks 12 and 52 were observed with mirikizumab vs placebo in IBDQ total and domain scores, SF-36 summary and domain scores, and EQ-5D-5L visual analog scale scores (all P < 0.001). Significant improvements with mirikizumab vs placebo were observed in Work Productivity and Activity Impairment:CD scores at week 12: absenteeism ( P = 0.001), presenteeism ( P = 0.005), activity impairment ( P < 0.001), and overall work impairment ( P = 0.002); these improvements were maintained at week 52 (all P < 0.001, except absenteeism). At weeks 12 and 52, a greater proportion of mirikizumab-treated patients vs placebo achieved IBDQ response, IBDQ remission, and clinically important improvement in physical and mental component summaries of SF-36 (all P < 0.001). DISCUSSION: Patients with moderately to severely active CD treated with mirikizumab reported clinically meaningful improvements in HRQoL and work productivity vs placebo at week 12, which were maintained at week 52.