Urinary tract calculi have been reported to account for between 1 in 1,000 and 1 in 7,600 hospital admissions in children in the USA. The annual incidence of urolithiasis in patients older than 10 years is 109 per 100,000 of the population in men and 36 per 100,000 of the population in women in Minnesota. The use of various medications is considered to be one of the etiologic factors of nephrolithiasis. Ceftriaxone is a widely used third-generation cephalosporin that is generally considered very safe, but complications such as biliary pseudolithiasis, and rarely, nephrolithiasis have been reported in children. There is limited information about urolithiasis as a side effect of ceftriaxone. The aim of this study was evaluation of the incidence of nephrolithiasis following ceftriaxone therapy in children. This quasi-experimental before and after study was conducted in Mofid Children's Hospital between 2003 and 2005. All patients were treated with 75 mg/kg intravenous ceftriaxone. Diagnosis of pyelonephritis was based on standard criteria. The first renal ultrasonography was performed on the first or second day of admission and was repeated on the last day of treatment. We also evaluated complicated patients for the third time with renal ultrasonography 3 months after treatment. Stone-forming patients underwent metabolic kidney stone risk factor evaluation. We evaluated 284 patients with pyelonephritis, 185 girls and 99 boys. The first ultrasonography was normal in all of our patients. On the second ultrasonography renal stones were reported in 4 out of 284 cases (1.4% and CI=0.96-1.83%). Underlying metabolic risk factors could not be identified in stone-forming patients. Follow-up ultrasonography 3 months later was normal. The results of our study suggest that ceftriaxone-treated patients may be at an increased risk of kidney stone formation. Stones passed spontaneously in all affected patients so the use of this effective drug can be safely continued. Close monitoring of ceftriaxone-treated patients with regard to kidney stone formation is recommended.