Objectives: Dextranomer/hyaluronic acid (Dx/HA) copolymer has favorable properties for endoscopic treatment of vesico-ureteral reflux (VUR). This open, randomized study was performed to compare the efficacy and safety of Dx/HA copolymer with antibiotic prophylaxis in children with VUR. Methods: Children >1 year of age with VUR grade II to IV (confirmed by voiding cysto-urethrogram) received endoscopic treatment with Dx/HA copolymer (n = 40) or 12 months of antibiotic prophylaxis (n = 21). Patients in the latter group with reflux grade ≥II at month 3 received a second implantation. All patients were reassessed by voiding cysto-urethrogram at month 12. Scintigraphy and ultrasound were performed to investigate renal status. Results: At month 12, 69% of patients in the Dx/HA copolymer group had reflux grade ≤I bilaterally, compared with 38% in the antibiotic group (P =.029). Of patients with reflux grade ≤I at month 3, 89% showed a sustained response at month 12. One serious adverse event was reported in the antibiotic prophylaxis group, but this was not attributed to study treatment. No other adverse events occurred. Conclusions: Endoscopic treatment with Dx/HA copolymer was more effective than antibiotic prophylaxis in alleviating childhood VUR, and there were no safety concerns with either treatment. (J Pediatr 2002;140:230-4)