The role of antimicrobial prophylaxis in vesicoureteral reflux (VUR) has come under increasing scrutiny because of better analytical methods in the published literature, knowledge gained from VUR and renal scars diagnosed without preceding urinary tract infection (UTI), and better renal imaging modalities for diagnosing renal scars. A meta-analysis of the five recent randomized studies with a total of 809 patients with VUR diagnosed after UTI reveals a relative risk of UTI recurrence of 0.82 [95% confidence interval (CI) 0.62-1.08; p = 0.16) with prophylaxis. A meta-analysis of the four studies with a total of 662 patients with UTI with and without VUR evaluated for renal scarring reveals a relative risk of 1.04 (95% CI: 0.84-1.30; p = 0.69), with prophylaxis. However, these observations need to be interpreted with caution because of the limitations with these studies and their heterogeneity for meta-analysis, particularly for renal scarring. More research is needed to validate the role of prophylaxis in VUR diagnosed after UTI, and even more research is warranted to answer the questions regarding antimicrobial prophylaxis across the spectrum of VUR in different clinical settings.