OBJECTIVES: Hospitalization is a major source of health care costs for Crohn's Disease (CD). This retrospective analysis of clinical trial data examined the relationship between Crohn's Disease Activity Index (CDAI) scores and hospitalization risk. METHODS: We analyzed data from the CHARM trial (adalimumab maintenance therapy) for 778 randomized patients (of 854 enrolled) with moderate to severe CD (baseline CDAI: 220–450) who were treated for up to 66 weeks. As a measure of clinical efficacy, CDAI scores were collected. Hospitalization events were recorded as severe adverse events. While controlling for patient demographic information, we applied a Cox proportional hazard regression model to evaluate the relationship between hospitalization risk and CDAI reduction or clinical remission (CDAI<150). CDAI and clinical remission were imputed as time-varying covariates. Simulation was applied to assess 1-year, all-cause and CD-related hospitalization rates. RESULTS: A total of 157 patients were hospitalized, of which 112 were for CD-related reasons. Cox regression revealed that, at any point in time, lower CDAI score was associated with decreased risk of both all-cause hospitalization (hazard ratio [HR]=1.06 for every 10 points of CDAI increase, p<0.01) and CD-related hospitalization (HR=1.08, p<0.01). Simulation study showed that a 70-point CDAI reduction throughout the follow-up period reduced all-cause hospitalization risk by 28.3% and CD-related hospitalization risk by 36.5% at year-end. Clinical remission was associated with a significant reduction in both all-cause (HR=0.52, p<.001) and CD-related hospitalizations (HR=0.37, p<.001). Simulations revealed that clinical remission was associated with a 43.7% decrease in the 1-year risk of all-cause hospitalization and a 60.3% decrease in CD-related hospitalization. CONCLUSION: Both lower CDAI score and clinical remission are associated with significantly reduced hospitalization risk for CD patients.