Background Proactive dosing based on drug monitoring of adalimumab has been reported to be associated with higher rates of clinical remission in children with Crohn’s disease (CD). We aimed to investigate whether proactive drug monitoring of infliximab (IFX) is associated with higher rates of endoscopic healing (EH) in paediatric patients with CD. Methods We conducted a nonblinded, randomized controlled trial of 112 children with CD who were biologic naïve and had responded to induction treatment with IFX at 4 centers in South Korea from July 2017 to November 2020. Patients were randomly assigned to groups that received dosing based on proactive monitoring or clinically based dosing. The primary endpoint was EH at 1 year treatment. Results The primary endpoint was achieved in 80.0% (40/50) of the proactive dosing group and 57.1% (28/49) of the clinically based dosing group (P = 0.025). Transmural healing was achieved in 37.8% (17/45) of the proactive dosing group and 30.8% (12/39) of the clinically based dosing group (P = 0.657). Sustained corticosteroid-free clinical remission was achieved in 89.5% (51/57) of the proactive dosing group and 70.9% (39/55) of the clinically based dosing group (P = 0.025). Sustained durability of infliximab was observed in 94.7% (54/57) of the proactive dosing group and 92.7% (51/55) of the clinically based dosing group (P = 0.714). Conclusion Dosing based on proactive monitoring was superior to clinically based dosing in terms of endoscopic healing in a randomized controlled trial of paediatric CD.