Objective: To determine whether the addition of a single dose of ceftriaxone sodium to a 10-day course of trimethoprim and sulfamethoxazole hastens urine sterilization or resolution of clinical symptoms in febrile children with urinary tract infections. Design: Prospective, single-blind, randomized study, Setting: Tertiary care children's hospital emergency department. Patients: Febrile children aged 6 months to 12 years with a presumptive urinary tract infection based on history, physical examination, and urinalysis findings. Interventions: A history was taken, a physical examination and urinalysis and culture were performed, and a white blood cell count and erythrocyte sedimentation rate were obtained. Children were randomized to receive an intramuscular dose of ceftriaxone then 10 days of trimethoprim-sulfamethoxazole (IM+PO group) or oral trimethoprim-sulfamethoxazole alone (PO group). After receiving study medication, patients were discharged from the hospital to return in 48 hours for a follow-up evaluation and urine culture. Treatment failure was defined as the persistence of a positive culture at 48 hours or the need for hospital admission for intravenous rehydration or antibiotic therapy. Results: Sixty-nine children were enrolled, 34 in the IM+PO group and 35 in the PO group. The 2 groups were similar at the initial visit with respect to age, sex, clinical degrees of illness, white blood cell count, and erythrocyte sedimentation rate (P>.05). At the 48-hour follow-up visit, there were no differences between the 2 treatment groups in resolution of vomiting, fever, general appearance, abdominal tenderness, and hydration state (P>.05). There were 9 treatment failures, 4 in the IM+PO group and 35 in the PO group (P=.93). Conclusion: The addition of a single dose of intramuscular ceftriaxone to a 10-day course of oral trimethoprimsulfamethoxazole for urinary tract infection with fever resulted in no difference at 48 hours in the urine sterilization rate, degree of clinical improvement, or subsequent hospital admission rate.