Background Single-balloon enteroscopy (SBE) has not been reported in pediatric Crohn's disease (CD). Objective To determine technical performance, yield, safety, and clinical impact of SBE in pediatric patients with suspected and established CD. Design Prospective, cohort study. Setting Academic tertiary-care referral center. Patients This study involved 16 patients (group A) with suspected CD and unspecific upper and lower GI endoscopy results and 14 patients (group B) with longstanding CD with previous surgery and showing signs unaccountable by conventional endoscopy. All underwent magnetic resonance imaging, and 14 patients in group A also underwent wireless capsule endoscopy. Intervention SBE. Main Outcome Measurements SBE diagnostic and therapeutic yield, technical performance, clinical impact, and safety. Results In group A, SBE aided diagnosis of CD in 12 patients and eosinophilic enteropathy in 2 patients, whereas no lesions were found in 2 patients. WCE was diagnostic of CD in 3 patients, suggestive of CD in 7 patients, and unspecific in the remaining patients. In group B, SBE revealed moderate-to-severe disease activity in most patients, leading to the introduction of or change in biological therapy, with a marked decrease in the pediatric Crohn's disease activity index scores. SBE allowed successful dilation of small-bowel strictures in 2 patients in group A and 3 in group B. No complications occurred. Limitations Small sample size, no direct comparison with imaging or other endoscopic techniques. Conclusion SBE is a useful and safe endoscopic procedure for evaluating the small bowel in pediatric patients with suspected or established CD. Not only does it allow a definite diagnosis of CD when the latter is uncertain, but it is also very effective in the management of small-bowel strictures, thus avoiding surgery. It may be helpful in redirecting therapy in selected CD patients.