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Enterocutaneous fistula (ECF) is a serious complication of Crohn's disease (CD). Enteral nutrition (EN) is believed as one of therapeutic strategies of CD. This study is dedicated to identify predictors of response to EN in CD, which may lead to a better selection of fistula patients for this therapy.Forty-eight CD patients with ECF treated with short-peptide-based EN for 3 months were included in this study. All patients were followed up for at least 6 months. Logistic regression was performed to investigate the potential predictors of response to EN in these patients.In total, 30 out of 48 patients were confirmed with a successful closure of fistula after 3 months’ EN therapy. The average closure time was 32.4 ± 8.85 days. Inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein (CRP) and platelet count) improved significantly after EN therapy in all enrolled patients. Specifically, the improvement of CRP after therapy in closed group was more important compared with that in unclosed group (P =0.035). Nutrition status (body weight, body mass index (BMI), hemoglobin, serum albumin (ALB), serum prealbumin and total protein (TP)) improved as well (P<0.05). Similarly, after treatment, the improvement of serum albumin (P = 0.046) and prealbumin (P =0.006) in closed group was much more important than those in unclosed group. Logistic regression analysis discovered that a decreased CRP level and an elevated BMI level would be beneficial to the response to EN in CD patients with ECF.In CD patients with ECF, lower CRP and higher BMI are associated with higher possibility of closure after EN treatment. EN therapy can lead to a closure of ECF in a certain proportion of patients. EN therapy could also ameliorate inflammatory condition and improve nutrition status.