OBJECTIVES: Vesicoureteral reflux (VUR) occurs in approximately 1% of infants and children and is associated with recurrent urinary tract infections (UTIs). Guidelines in the treatment of VUR target reducing the number of UTIs in patients with VUR. Treatment strategies include antibiotic prophylaxis, which is the current first-line treatment, as well as endoscopic injection and surgery. The objective of this study is to examine the use of endoscopic injection with dextranomer/hyaluronic acid (Dx/HA) as a curative option and as an alternative to antibiotic prophylaxis as it is gaining in popularity in the treatment of VUR. METHODS: The nationally representative PharMetrics Integrated Medical and Pharmaceutical database was used to conduct this retrospective analysis. Patients <11 years of age who were continuously eligible with an International Classification of Diseases (ICD)-9-CM for VUR were identified. Resource utilization and outcome measures were evaluated over a 6-month pre- and 12-month post-index period. As randomization is not possible in a retrospective database analysis, patients were matched 3:1, antibiotic prophylaxis to Dx/HA, by age, gender, urinary tract infections (UTIs) prior to index date, and diagnosing physician specialty. The primary outcome assessed was UTIs. RESULTS: Of the patients, 114 received a prescription for antibiotic prophylaxis and 38 underwent endoscopic injection with Dx/HA between January 2000 and December 2004. The average number of UTIs per year was 0.28 in the antibiotics cohort and 0.08 in the Dx/HA cohort, respectively. The incidence rate ratio (IRR) of 4.826 (P = 0.029) revealed that the average number of UTIs was 3.83 times greater for patients receiving antibiotic prophylaxis compared with patients who underwent endoscopic injection. CONCLUSION: Treatment with endoscopic injection with Dx/HA resulted in significantly fewer UTIs compared with children receiving antibiotic prophylaxis, supporting a role for Dx/HA as a first-line treatment option for patients with VUR.