Background The optimal target anti-TNF drug level that correlates with control of intestinal inflammation in IBD patients is still poorly defined. We aimed to define infliximab and adalimuamb serum levels that distinguish patients with mucosal healing (MH) from those with ongoing inflammation. Methods We conducted a retrospective study of 135 IBD (107 Crohn's disease, CD, 28 ulcerative colitis, UC) patients treated with infliximab (n=75) or adalimumab (n=60) maintenance therapy, who underwent lower endoscopy at a tertiary medical center. Infliximab/adalimumab drug levels were measured in temporal relation to endoscopy, and correlated with inflammatory markers (CRP) and with endoscopic evaluation of disease activity (SES-CD and MAYO scores for CD and UC respectively). Results Median drug levels (DL) were significantly higher in patients withMH vs. patients with endoscopically active disease, for both infliximab and adalimumab therapy (4.3 vs. 1.15 μg/ml, p=0.0002, 6.2 vs. 3.1 μg/ml, p=0.044, respectively). Patients whose CRP normalized under treatment, similarly had higher median DL than those who did not (4 vs. 2 μg/ml, p=0.022 for infliximab, 5.7 vs. 2.2 μg/ml, p=0.015 for adalimumab, respectively). Infliximab DL above 5.8 μg/ml (AUC=0.75, p<0.0001) and adalimumab levels above 7.4 μg/ml (AUC=0.68, p= 0.03) had 85% specificity for achieving MH. Incremental gain analysis demonstrated that 50% of patients achieved MH when infliximab serum levels were above 4μg/ml and 75% reached MH with levels above 8μg/ml, whereas for adalimumab 50 and 75% of patients achieved MH when DL were above 7.5 and 10mcg/ml, respectively. Higher anti-TNF levels (infliximab DL above 8μg/ml or adalimumab DL above 10mcg/ml) were associated with only a negligible incremental increase of MH percentage.Conclusions Infliximab and adalimumab serum levels were significantly associated with MH. Infliximab DL above 5.8μg/ml and adalimumab DL above 7.4μg/ml had 85% specificity for MH, whereas increasing infliximab DL above 8μg/ml or adalimumab DL above 10mcg/ml conferred little additional endoscopic benefit.