Abstract Background Objective goals are needed to guide patient management and assess treatment efficacy in patients with Crohn’s disease (CD). Bowel ultrasound (US) is a widely available, non-invasive and inexpensive technique increasingly being used in these patients. The use of bowel wall thickness (BWT) has been proved to be an accurate measure for assessing disease activity and response to therapy. Recent studies show a rapid improvement of BWT after 3-month of therapy. Our aim was to evaluate BWT variation after induction therapy with infliximab (IFX) in CD patients and correlate BWT with clinical and laboratory parameters. Methods Prospective cohort multicentre study including patients with active CD starting IFX therapy. Clinical disease activity was assessed using the Harvey–Bradshaw index (HBI). C-reactive protein (CRP) and faecal calprotectin (FC) were measured both at week 0 and after induction therapy (week 14), and infliximab trough levels (ITL) were measured at week 14. Bowel ultrasound was performed at week 0 and 14, BWT from the worst segment was selected for analysis. Abnormal BWT was defined has higher than 3mm in any bowel segment. Results We included 10 patients with CD (80% males; median age 29 (21–64) years). According to Montreal classification, most patients were A2 (7/10), had ileocolonic disease (L1 20%; L2 20%; L3 60%) and an inflammatory phenotype (B1 60%; B2 20% and B3 20%). Most patients were anti-TNF therapy naive (80%), and combination therapy was used in 80%. Before IFX (week 0) median HBI was 2 (IQR 1.75–5.25), CRP 1.10 mg/dl (IQR 0.65–3.50) and FC 802 μg/g (IQR 324–1336). The terminal ileum was the most affected segment identified by the USA (5/10), followed by ascending colon (2/10) descending colon (2/10) and sigmoid colon (1/10). Median BWT was 4.6 mm (IQR 3.6–6.4). After induction therapy (week 14), all patients were in clinical remission (HBI<5) except for one in whom IFX dose was increased to 10 mg/kg. Laboratory remission (CRP < 0.5 mg/dl and FC < 250 μg/g) was present in 50% of patients. US response (measured by a reduction in BWT of at least 0.5 mm) was observed in 70% of patients, with US remission (normalisation of BWT in the most affected segment) in 30%. At week 14, 70% of patient had ITL > 3 μg/ml. Median BWT at week 14 was higher in patients with ITL < 3 μg/ml (6.25 vs. 2.98 mm, p = 0.048). Conclusion The majority of our patients showed a US response (reduction in BWT) after 14 weeks of infliximab, suggesting that reduction in BWT could be an early marker of response to therapy. US evaluation after induction therapy can be a helpful tool to monitor disease activity and guide patient management in CD patients in our daily practice.