Dextranomer/hyaluronic acid (Dx/HA) copolymer has been used widely for the treatment of vesicoureteral reflux (VUR) in children since 2001. However, the factors that influence the outcome of injection therapy with Dx/HA have remained unclear. In this study, we retrospectively evaluated the outcomes in 101 consecutive children to determine the cure and to identify the factors that can impact treatment outcomes of Dx/HA injection. Endoscopic treatment with Dx/HA was performed in 133 ureters, in 101 patients with grade III-V VUR. Of the patients, 68 (67.3%) were girls and the mean age was 6.5 years. Before and after the treatment, the presence and grades of VUR were determined by voiding cystourethrograms. The patients' age, gender, laterality, preoperative reflux grade, ureteral duplication, morphology of ureteral orifice, renal hypoplasia and experience with surgery were assessed as predictive factors related to the success rates of Dx/HA injection therapy. The cure rates were 54.8% after the first injection, 66.9% after the second and 73.6% after the third injection. Patients with a high grade (grade IV or V), duplicated system, golf hole-shaped orifice and renal hypoplasia had significantly lower cure rates (P < 0.05). Experience with the technique also correlated with the positive outcome of the procedure. New contralateral vesicoureteral reflux developed in five (7.2%) patients with unilateral VUR, and all of them resolved spontaneously during the first year of followup. No treatment-related significant complication was encountered. Although, endoscopic treatment of VUR with Dx/HA provides a high rate of success in children with medium or high grade VUR, treatment failure may be seen in some patients. However, we showed that endoscopic treatment with Dx/HA was effective in selected patients with grade V VUR, and we emphasize the need for further large-scale studies to confirm our findings.