Very early-onset inflammatory bowel disease (IBD) and specifically infantile-onset IBD patients, are characterized by high rates of extensive colonic involvement and decreased response rate to standard therapeutic regimens, including infliximab (IFX). We present a case series of 4 patients with infantile-onset IBD achieving clinical and biologic remission, after treatment with therapeutic drug monitoring (TDM)-guided accelerated high-dose IFX therapy. All patients were treated with accelerated high-dose IFX induction of up to 22 mg/kg. In 3 of these patients, accelerated high-dose IFX was used following failure of intensified standard dose induction. All patients achieved remission following re-induction.We suggest that children with infantile-onset IBD may require a TDM-guided accelerated high-dose IFX induction and maintenance treatment in order to achieve and maintain remission. Personalized approach in these patients is essential in order to prevent underdosing and to avoid inappropriate interpretation of treatment failure.