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Endoscopic recurrence is associated with a risk of clinical recurrence in patients with Crohn's disease after ileocecal or small bowel resection. Drug levels and presence of antidrug antibodies are associated with important clinical and endoscopic outcomes in patients with Crohn's disease treated with tumor necrosis factor inhibitors, such association was not evaluated for endoscopic postsurgical recurrence.Consecutive patients with Crohn's disease treated with anti–tumor necrosis factors after surgery were identified in the databases of the participating centers. Anti–tumor necrosis factor levels and antidrug antibodies were correlated with Rutgeerts score on colonoscopy performed ≥6 months postoperatively. Significant endoscopic recurrence (SER) was defined as Rutgeerts score >2.Seventy-three consecutive patients (32-infliximab, 41-adalimumab) were included in the study. The colonoscopies were performed after a median of 15 (7–43) months after surgery and 8 (6–15) months from treatment onset. SER was demonstrated in 26/73 (35.6%) of the patients. The need for dose optimization, as well as trough infliximab levels (2.4 μg/mL [0.45–4.1] versus 1.1 (0–0.6), P = 0.008) and presence of antidrug antibodies (1/18 [5.6%] versus 10/14 [71.4%], P = 0.0001) were significantly associated with a risk of SER. The optimal cutoff infliximab level for prediction of SER was 1.8 μg/mL. No association between adalimumab levels and antiadalimumab antibodies was demonstrated.