Long-term, low-dose prophylactic antibiotics are commonly given to children with urinary tract infections (UTI) to prevent recurrences and ultimately to prevent renal damage. The evidence for the efficacy of this practice, however, has been mixed. A new large randomized trial provides strong evidence that preventive antibiotics are effective in reducing the incidence of symptomatic bacterial UTIs (level 1 [likely reliable] evidence). A total of 576 children (median age 14 months) with at least 1 UTI (42% with vesicoureteral reflux) were randomized to a suspension of trimethoprim 2 mg/kg plus sulfamethoxazole 10 mg/kg (Bactrim, Septra) vs. placebo daily for 12 months. Symptomatic UTI, defined as symptoms plus positive urine culture, occurred in 13% of the antibiotic group vs. 19% of the placebo group (p = 0.02, NNT 17) (N Engl J Med 2009 Oct 29;361(18):1748). This study did not have sufficient power or follow-up duration to determine whether UTI prophylaxis is more effective than simply treating symptomatic infections as they occur for the prevention of long-term renal damage.