Endoscopic correction of vesicoureteral reflux has become an established alternative to long-term antibiotic prophylaxis and ureteral reimplantation. A number of tissue augmenting substances have been used for the endoscopic correction of vesicoureteral reflux. We prospectively evaluated the effectiveness of dextranomer/hyaluronic acid copolymer (Deflux) as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2004, 692 children with a median age of 2.1 years (3 months to 13.7 years) with high grade vesicoureteral reflux underwent endoscopic subureteral injection of Deflux soon after the diagnosis of vesicoureteral reflux was made on the initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 283 patients and bilateral in 409. Of the 1,101 ureters vesicoureteral reflux was grade II to V in 35 (3.2%), 580 (52.7%), 457 (41.5%) and 29 (2.6%), respectively. The procedure was performed on an outpatient basis. Followup ultrasound and voiding cystourethrogram were performed 3 months after the procedure, and renal and bladder ultrasound was done annually. Reflux resolved after first, second and third endoscopic Deflux injections in 952 (86.5%), 130 (11.8%) and 19 ureters (1.7%), respectively. Followup ultrasound revealed no evidence of delayed vesicoureteral junction obstruction. Of the patients 18 (2.6%) had urinary tract infection during followup after successful vesicoureteral reflux correction. Endoscopic subureteral injection of Deflux is excellent first line treatment in children with high grade vesicoureteral reflux. This 15-minute outpatient procedure is safe and simple to perform, and it can be easily repeated in failed cases.