Introduction: We assessed the effect of adalimumab dose escalation on risk of hospitalization in patients with moderately to severely active UC who did not respond or lost response after adalimumab induction therapy. Methods: Data were pooled from two randomized, double-blind, placebo-controlled phase 3 trials of adalimumab in patients with moderately to severely active UC (ULTRA 1 and 2: NCT00385736; NCT00408629). Patients randomized to adalimumab 160/80 mg induction therapy at weeks 0/2 followed by adalimumab 40 mg EOW who later dose escalated to 40 mg every week owing to non-response or loss of response were included in the analysis. Kaplan-Meier time-to-event analysis was used to estimate observed risks of all-cause and UC-related hospitalization within 90 days after dose escalation. Cox proportional hazards models were used to establish the relationship between hospitalization (both all-cause and UC-related) and partial Mayo scores after dose escalation, controlling for age, sex, prior anti-tumor necrosis factor (anti-TNF) status (naive or experienced), and partial Mayo score before dose escalation. This model's coefficients were then used to predict the 90-day all-cause and UC-related hospitalization risks had no dose escalation occurred, by assuming no changes in patients' partial Mayo scores in the period after dose escalation vs before dose escalation. Results: Of 122 patients who escalated to weekly adalimumab dosing, the majority were male (68%) and naive to anti-TNF agents (74%); mean age was 39.5 years and mean UC duration was 8.3 years. Mean partial Mayo score decreased from 6.8 before dose escalation to an average of 5.17 after dose escalation. For patients who dose escalated, the observed (Kaplan Meier) 90-day all-cause and UC-related hospitalization risks were 8.7% and 6.7%, respectively. The predicted 90-day all-cause and UC-related hospitalization risks, had patients continued on EOW therapy, were 13.0% and 10.3%, respectively. The relative risk of both all-cause and UC-related hospitalization in patients who dose escalated was lowered by 33.2% and 35.5%, respectively, compared with the predicted risk without dose escalation, reflecting the benefits of dose adjustment. Conclusion: Dose escalation of adalimumab in patients with moderately to severely active UC who did not respond or lost response after induction therapy reduced the 90-day risk of hospitalization and reflected a benefit of adalimumab dose escalation for treating these UC patients.