BACKGROUND Switches between anti-tumor necrosis factor agents in the treatment of Crohn's disease (CD) occur in case of treatment failure, intolerance, or patient preference. No data are currently available on the usefulness of a second infliximab treatment after earlier discontinuation and previous switch to an alternative anti-tumor necrosis factor agent. In this study, we evaluated the clinical benefit of infliximab retreatment in patients with CD after sequential use of both infliximab and adalimumab. METHODS Twenty-nine patients with CD who had received earlier treatments with sequential infliximab and adalimumab and were then restarted on infliximab were retrieved from a multicenter registry designed for the follow-up of adalimumab treatment for CD. Short-term and sustained effects of infliximab retreatment were evaluated retrospectively by reviewing clinical records. Follow-up was 18 months for all patients. RESULTS In 13/29 (45%) patients, infliximab was reintroduced at intensified dosing schedule (>5 mg/kg or <8 wk) for 23/29 (79%) of patients similar to the schedule who were on at time of previous discontinuation. During the second infliximab treatment course, dosing was further intensified in 11 out of 29 (38%) patients. After 18 months 18/29 (62%), patients were still on continued therapy of their second infliximab treatment. Infliximab was discontinued (after a median of 7 mo) in 11 out of 29 patients for loss of response (n = 7 [24%]), intolerance (n = 3 [10%]), or non-compliance (n = 1 [3%]). Use of induction schedule or concomitant immunomodulators were not significantly associated with treatment benefit. CONCLUSIONS The majority of patients with CD benefit from a second treatment with infliximab after previous treatment with infliximab and adalimumab, which offer a meaningful therapeutic option in often highly refractory patients.