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Adequate infliximab (IFX) levels are associated with favorable outcomes in inflammatory bowel disease. Using therapeutic drug monitoring (TDM) to guide dosing is cost effective and associated with clinical improvement, but effect on endoscopic outcomes remains unclear.Primary responders to IFX who underwent dose escalation (2008–2014) were reviewed. Patients with active endoscopic disease were included. Two cohorts were examined: TDM-based decision to escalate (TDM) and clinical decision (non-TDM). Outcomes recorded at median 6 months after adjustment included endoscopic remission (Mayo <1, Simple Endoscopic Score for Crohn's Disease <3), C-reactive protein, and inflammatory bowel disease–specific health care utilization. Postadjustment IFX and antibodies to infliximab levels discriminant for endoscopic remission were determined. Multivariable regression evaluated independent predictors of remission.Of note, 312 dose optimizations were examined (149 TDM and 163 non-TDM). Clinically, groups were similar. Sixty-three percent TDM attained postadjustment endoscopic remission compared with 48% non-TDM (P < 0.05). Sixty-nine percentage TDM had significant clinical response (57% non-TDM [P < 0.01]); fewer were hospitalized (22% TDM versus 35% non-TDM, P = 0.025). Patients with ulcerative colitis had shorter time to escalation (10 versus 20 mo, P < 0.0001). Median IFX levels increased after escalation in TDM (1.5 [pre] and 11 μg/mL [post]; P < 0.0001) and were higher than non-TDM postadjustment levels (11 versus 6.5 μg/mL, P = 0.015). Postadjustment IFX >4.5 μg/mL (area under curve = 0.8; 95% confidence interval, 0.71–0.88) and antibodies to infliximab <3.3 U/mL (area under curve = 0.70; 95% confidence interval, 0.63–0.81) were associated with endoscopic remission. Multivariable analysis showed that IFX concentration (odds ratio 1.2 [95% confidence interval, 1.1–1.3]; P < 0.0001) remained an independent predictor of endoscopic remission.TDM before dose adjustment is associated with higher postadjustment levels and endoscopic remission.