Background: Inadequate response to infliximab IFX therapy in Crohn’s disease CD may necessitate dose intensification. We evaluated safety and efficacy of high-dose IFX HD IFX greater than 10mg/kg every 8 weeks in CD and characterized predictors of response to HD IFX intensification. Methods: Electronic medical records were queried for CD patients between 2010 and 2012 who received HD IFX and were reviewed for history, medications, laboratory data, efficacy, and safety. Results: In all, 86 patients received HD IFX for CD at doses between 10 and 22.5mg/kg every 4 to 7 weeks. In early HD IFX therapy week 1–16, 25.8% and 59.1% experienced full and partial response, respectively. In later HD IFX therapy week 38–100, 27.9% and 34.4% experienced full and partial response, respectively. Median serum IFX levels increased from 1.7 to 7.3µ/mL p = 0.017, and median C-reactive protein CRP values decreased from 20.5 at baseline to 4.7mg/L after 16 weeks p < 0.001. Baseline CRP values were significantly elevated in the group that responded at 1–16 weeks compared with nonresponders 22.0 vs 3.5mg/L, p < 0.01. HD IFX therapy was discontinued in 26% and 7.3% of patients for inadequate response and adverse events, respectively. Eleven cases of infection required hospitalization for a serious infection rate of 7.41 events per 100 patient-years. Conclusions: HD IFX therapy may benefit CD patients who have failed standard doses of IFX. HD IFX therapy may be associated with more serious adverse events compared with standard dosing. Baseline CRP value may predict clinical response to HD IFX.