Since DX/HA was approved by the Food and Drug Administration in 2001 as an acceptable tissue-augmenting substance for subureteral injection, endoscopic treatment has become increasingly popular for treating vesicoureteral reflux (VUR). However, most paediatric urologists still continue to recommend ureteral reimplantation as the treatment of choice in the management of grade V VUR. The purpose of this study was to prospectively evaluate the effectiveness of endoscopic subureteral injection of DX/HA in the treatment of grade V reflux. During 2001-2009, 56 children (35 males, 21 females) with primary grade V VUR underwent endoscopic treatment using DX/HA. Their ages ranged from 4 months to 11 years. Forty-nine patients had unilateral grade V VUR, and seven had bilateral grade V (63 refluxing ureters including 17 duplex systems). Renal scarring on dimercaptosuccinic acid was observed in 39 kidneys (mild scarring 13, moderate scarring 14 and severe scarring 12). In all patients, endoscopic injection was made after inserting the needle within the wide ureteral orifice. Renal ultrasound and voiding cystourethrogram was performed 3 months after the endoscopic treatment. If VUR had not resolved, the patient was considered for further endoscopic treatment. After the VUR was resolved, children were followed with renal ultrasound at 1 year and every 2 years thereafter. The VUR completely resolved after first injection of DX/HA in 33 (52.4%) ureters and downgraded to grade I VUR in 7 (11.1%) ureters. 19 (30.2%) ureters required a second injection, and 4 (6.3%) ureters required a third injection to resolve VUR. No children in this series needed reimplantation of ureters or presented with ureteral obstruction during follow-up. Endoscopic treatment with DX/HA is effective in eradicating grade V primary reflux. This simple and minimally invasive treatment should be offered to all parents of children with grade V VUR as an alternative to ureteral reimplantation.