Purpose Dx/HA copolymer was approved by the Food and Drug Administration in 2001 for the treatment of VUR in children. Published results have varied widely, prompting us to report our single center experience with 300 consecutive patients. Materials and Methods All patients undergoing Dx/HA injection (300 children, median age 5.4 years) at our institution were eligible for this study. We examined several parameters to determine which variables influence the success of Dx/HA injection, including preoperative reflux grade, bladder diverticula, neurogenic bladder, ureteral duplication, perioperative urinary tract infection, dysfunctional voiding, laterality of reflux and amount of Dx/HA injected. Results A total of 225 patients (75%) underwent postoperative studies, and, thus, were eligible for study inclusion. Reflux was cured in 144 patients (64%) and improved in 44 (20%). A total of 20 patients had ureteral duplication anomalies. Cure rates in this subgroup were significantly decreased compared to nonduplicated cases (40% vs 66%). Injection in low grade (I to II) reflux was significantly more successful than in high grade (III to IV) reflux (72% vs 54%). A total of 10 patients (8.3%) with unilateral reflux had development of de novo contralateral reflux. Of the patients who failed initial injection 10 (4%) underwent repeat injection, of whom 5 (50%) were cured after the second injection. Two patients (0.9%) had development of temporary ureteral obstruction. Conclusions We report a large short-term single center experience with endoscopically injected Dx/HA. Although our cure rate of 64% was less than published rates for open surgery, the minimal morbidity and low complication rate of endoscopic treatment make it an attractive first line therapy for patients with VUR. Longer followup is required to better evaluate this technique.