BACKGROUND: Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled data from 52-week Phase III maintenance trials of risankizumab and upadacitinib in patients with moderate-to-severe active CD. METHODS: Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission was defined as a Simple Endoscopic Score for Crohn's Disease (SES-CD) of no greater than 4, with at least a 2-point reduction vs induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm. RESULTS: Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with incidence rate ratios of 0.45 (95% confidence interval [CI], 0.22-0.95, p = 0.036) and 0.71 (95% CI, 0.44-1.14, p = 0.156) for long-term disease-related and all-cause hospitalizations, respectively. CONCLUSIONS: Week 12 endoscopic remission is independently associated with a reduction in 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.