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Both thiopurines and anti-tumor necrosis factor (TNF) α agents are effective for treating Crohn’s disease (CD) as they can induce clinical remission (CR) and mucosal healing (MH) in most patients. Nevertheless, data on transmural healing (TH) induced by thiopurines and anti-TNF-α agents are still lacking. This study aimed to explore the rate of TH evaluated by bowel sonography in patients with CD treated with biologics and immunosuppressors and its correlation with CR and MH.We performed an observational longitudinal study evaluating TH, CR, and MH in all patients with CD attending our clinic who would complete 2 years of maintenance treatment with biologics or thiopurines. CR and MH were assessed in accordance with current literature, whereas TH was recorded using bowel sonography. All patients underwent endoscopy and bowel sonography before starting treatment and 2 years later.The study included 66 patients with CD treated with biologics and 67 patients receiving thiopurines. Finally, TH was present in 17 patients on biologics and only 3 patients treated with thiopurines (25% versus 4%; P < 0.01; odds ratio = 6.2). CR was achieved in 37 patients on biologics and in 34 patients on thiopurines (59.7% versus 53%; P = not significant), whereas MH was more frequent in patients treated with anti-TNF-α agents even though without statistical significance (38% versus 25%; P = not significant).TH can be achieved in approximately 25% of patients with CD treated with anti-TNF-α agents and significantly correlates with MH. Further studies are needed to define the potential role of TH as long-term prognostic factor.