It is very important to treat patients with upper urinary tract infections (UTIs) promptly and effectively because of the potential sequelae. In the present study we compare the efficacy of the two cephalosporins, ceftriaxone and cefotaxime, in childhood pyelonephritis. The study protocal included 10 days of drug therapy. Both in patients receiving ceftriaxone and cefotaxime, successful eradication was achieved at the second day of therapy. The overall cure rate was significantly better in the ceftriaxone group than the cefotaxime group in terms of recurrence and reinfections (p < 0.05). Furthermore, in the complicated group, ceftriaxone was slightly superior to cefotaxime, approaching significance in terms of preventing recurrent infections. No serious adverse effects were observed in either of the groups. The present study has shown that ceftriaxone exhibits favorable clinical and bacteriologic efficacy in patients with complicated and uncomplicated upper UTI. Once-daily injection of ceftriaxone in children is also an attractive advantage of the drug when compared to twice-daily cefotaxime.