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Background: It remains unclear whether visceral adipose tissue (VAT) can predict the response of patients with Crohn’s disease (CD) to anti-tumour necrosis factor-α (anti-TNF-α) therapy. Objectives: This study aimed to investigate whether VAT predicts the efficacy of infliximab (IFX) for different sites of CD and its relationship with serum TNF-α levels and IFX serum trough concentration. Design: This is a multicentre retrospective study. Methods: Patients with CD treated with IFX from January 2014 to January 2021 were included. The perimeter of the visceral adipose area was obtained by a Computed Tomography (CT) scan. Participants were classified according to the lesion site (L 1 , L 2 , and L 3 ) and visceral fat area. The participants were divided into colon-uninvolved non-visceral obesity (L 1 -VAT L ), colon-uninvolved visceral obesity (L 1 -VAT H ), colon-involved non-visceral obesity (L 2 + L 3 -VAT L ), and colon involved visceral obesity (L 2 + L 3 -VAT H ) groups. The end points of this study were set as disease remission status at 6 and 12 months. Results: The final cohort included 140 patients. Regarding efficacy at 6 and 12 months, there was a significant difference between L 1 -VAT L (73.8% versus 36.8%, p = 0.006) and L 1 -VAT H (81.0% versus 47.4%, p = 0.008) groups. In the analysis of serum TNF-α levels and IFX serum trough concentrations, there was a significant difference between L 1 -VAT L and L 1 -VAT H (59.5 pg/mL versus 236.0 pg/mL, p TNF-α = 0.006), (10.0 μg/mL versus 0.4 μg/mL, p IFX = 0.000), and L 1 -VAT H and L 2 + L 3 -VAT H (78.7 pg/mL versus 118.6 pg/mL, p TNF-α = 0.031), (0.4 μg/mL versus 6.40 μg/mL, p IFX = 0.017). Conclusion: In L 1 patients, the VAT level predicted the efficacy of IFX, with high VAT values indicating poor efficacy. The VAT level may be a useful radiological marker to predict the efficacy of IFX in patients with various types of CD.