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Interleukin (IL)-9 drives gut inflammation, but its role in Crohn's disease (CD) is unclear. We aimed to analyze correlations between serum IL-9 levels and disease severity and to evaluate their predictive value in relation to the clinical efficacy of infliximab (IFX) in patients with CD.Between January 2013 and December 2015, 100 consecutive patients with active CD and 50 age- and sex-matched control individuals were recruited from a tertiary center. Their serum IL-9 levels were measured using an enzyme-linked immunosorbent assay. Correlations between the serum IL-9 levels and disease severity were examined. The serum IL-9 level was explored as a predictor of clinical remission and mucosal healing at week 30 in 50 patients for whom IFX therapy was administered.The serum IL-9 levels were significantly higher in the patients with active CD (22.0 pg/mL) than in the control individuals (6.3 pg/mL) (P < 0.001); they differed according to disease severity (moderate-to-severe CD: 29.1 pg/mL versus mild CD: 12.9 pg/mL) (P < 0.001), and they correlated well with the clinical activity of CD. IFX lowered the serum IL-9 level in patients who achieved efficacy at week 30. The areas under the curves for the IL-9 levels at weeks 14 and 30 that could predict clinical remission and mucosal healing at week 30 were 0.803 and 0.752 and 0.746 and 0.781, respectively.Serum IL-9 levels correlate with disease severity and the clinical efficacy of IFX in patients with CD, and IL-9 may be a promising novel biomarker for CD monitoring.