BACKGROUND: Proactive drug monitoring in our national cohort of children with inflammatory bowel disease suggested that 5 mg/kg dosing of infliximab (IFX) was associated with inadequate trough levels (TLs), thus we commenced empiric 10 mg/kg dosing in 2019. METHODS: This was a retrospective study of patients commenced on 5 or 10 mg/kg IFX between 2018 and 2020. The primary outcome was pre-fourth TL >/=5 microg/mL. Data source verification and analysis were undertaken retrospectively. RESULTS: During the study period, 122 patients were commenced on IFX and eligible for inclusion. Of these, 72% were male, 76% had Crohn's disease (CD), 23% had ulcerative colitis; mean (standard deviation [SD]) age at diagnosis was 11.8 (2.7) years; 60 commenced 5 mg/kg. Baseline parameters were comparable between groups. Fewer patients in the 5 mg/kg than 10 mg/kg group had pre-fourth TLs >/=5 microg/mL (6/48 [12.5%] vs 28/50 [56%], P < .001; mean [SD] TL 3.5 [6.3] vs 10.0 [9.9], P < .001). The 5 mg/kg group was less likely to have target pre-third TLs (6% vs 80%, P < .001); more likely to have treatment escalation (78% vs 45%, P < .001), and less likely to de-escalate (10% vs 29% P = .008). Proactive therapeutic dose monitoring (TDM) was practiced throughout the study period and mean (SD) IFX exposure per kg/week was similar in both groups by 1 year (1.4 [0.43] vs 1.56 [0.56] mg/kg/week, P = .137), as were infliximab durability and clinical outcomes. CONCLUSIONS: Our real-world data show that 5 mg/kg infliximab induction does not achieve target TLs in most children with CD. Higher-dose regimens should be considered, especially if proactive therapeutic drug monitoring is not available.