OBJECTIVE To determine the role of duodenogastro-esophageal reflux (DGER) in the pathogenesis of refractory gastro-esophageal reflux disease (GERD) in children. METHODS Twenty-two patients (12 boys, mean age, 13.2 years) with GERD symptoms that persisted on omeprazole (1 mg/kg) underwent upper gastrointestinal endoscopy and barium x-ray, 24-hour pH and DGER (Bilitec) monitoring, and a 13C octanoic acid gastric emptying breath test. RESULTS Patients presented mainly with epigastric pain, regurgitation, and nausea. Endoscopy revealed persistent esophagitis in 15 patients (68%). Pathologic acid and DGER exposure were present in 12 (55%) and 15 (68%) children, respectively, with combined pathologic reflux in 10 (45%). Acid exposure did not differ according to the presence of esophagitis, but patients with grade II esophagitis had significantly higher DGER exposure than those without esophagitis (9.1 +/- 5.3% vs 26.7 +/- 10.9% of the time, P < .05). Gastric emptying rate was not associated to acid or DGER exposure or persisting esophagitis. Symptoms improved after adding a prokinetic drug to the proton pump inhibitor therapy or referral for surgery (n = 5). CONCLUSIONS DGER may play a role in the pathophysiology of proton pump inhibitor-refractory GERD and esophagitis in children.