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Tumor necrosis factor (TNF) antagonists can induce mucosal healing in patients with Crohn’s disease (CD), but the effects on transmural inflammation and stenotic lesions are largely unknown.We performed a retrospective study in 50 patients (54% female, median age 37 yr) with CD who had undergone serial magnetic resonance imaging (MRI) examinations while receiving infliximab or adalimumab. Patients were grouped as clinical responders or nonresponders based on physician’s assessment, laboratory, and endoscopic appearance. MRI scoring was performed by 2 radiologists in consensus blinded to clinical data using a validated MRI scoring system. In total, 64 lesions on MRI were identified for analysis. Analyses were performed using paired t test and Wilcoxon rank test.During anti-TNF treatment, MRI inflammation scores improved in 29 of 64 lesions (45.3%), remained unchanged in 18 of 64 lesions (28.1%), or deteriorated in 17 of 64 lesions (26.6%) over time. In the anti-TNF responder group, the mean intestinal inflammation score of all lesions improved from 5.19 to 3.12 (P < 0.0001). The mean inflammation scores in stenotic lesions in anti–TNF responders also improved significantly, from 6.33 to 4.58 (P = 0.01). In contrast, the mean inflammation scores did not change significantly (5.55–5.92, P = 0.49) in nonresponders. Diagnostic accuracy of anti–TNF response on MRI was 68%.Improved inflammatory activity on serial MRI scans was observed in patients with clinical response to medical therapy with anti-TNF agents in luminal CD. MRI can be used as a complementary approach to measure transmural inflammation in patients with CD and guide the optimal use of TNF antagonists in daily clinical practice.