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BACKGROUND AND AIMS Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD. METHODS We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain pre-determined trough concentration, regardless of disease activity) with conventional management (clinically-driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using GRADE. RESULTS On meta-analysis of nine RCTs (eight RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709, 38%) vs. conventional management (292/696, 42%) (RR,0.96 [95% CI, 0.81-1.13]) with moderate heterogeneity (I2=36%) (GRADE; low certainty evidence), with no differences in patients with Crohn's disease (RR,0.87 [0.66-1.15]) and ulcerative colitis (RR,0.88 [0.72-1.07]). Disease duration, concomitant immunomodulators, disease activity at baseline and optimization of therapy prior to randomization did not modify this association. No differences were observed in risk of developing anti-drug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR,1.56 [1.25-1.94]). CONCLUSIONS Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations.