In order to evaluate the clinical efficacy and safety profiles of single-dose ceftriaxone (50 mg/kg, not exceeding 1 g) and a 10-day course of amoxicillin-clavulanate (amoxi-clav) [45 mg/kg/day, in 3 divided doses] in children with acute otitis media (AOM), we conducted a prospective, comparative, randomized trial. Between February 2000 and April 2002, 110 children with a mean age of 30.73 +/- 20.79 months were enrolled. 109 patients were evaluated for the safety assessment. The intent-to treat population included 96 patients who completed at least 3 days of treatment. The standard analysis population included 73 patients who completed the 10-day treatment period without any major violation. For the standard analysis population, 57 out of 73 patients experienced treatment success; 31 out of 41 patients in the ceftriaxone group were cured compared with 25 out of 32 patients in the amoxi-clav group. The rate of persistence of middle-ear fluid did not differ between the 2 groups at day 11 or day 28. A higher treatment preference rate was observed in the ceftriaxone group (93.9% vs 58.6%). The most common drug-related adverse effects were found in the digestive system, skin and appendages in both treatment groups. A single dose of ceftriaxone is as safe and effective as amoxi-clav for curing patients with acute otitis media. In addition, a substantially higher proportion of patients receiving single-dose ceftriaxone showed a preference for the study medication compared with those treated with amoxi-clav for 10 days.