This phase III, single-blind, randomized, multicentre clinical trial compared the safety and efficacy of clarithromycin and amoxycillin in the treatment of otitis media in pediatric patients. Two hundred and fifty-nine patients aged 1-12 were prescribed suspensions of clarithromycin (132 patients) or amoxycillin (127 patients). Both suspensions were prescribed at a dose of 125 mg for children weighing less that 25 kg or at 250 mg for children weighing more than 25 kg, but three doses of amoxycillin per day were given, while only two doses clarithromycin per day were required. Each drug was administered for approximately 5 days. Clinical evaluations were performed pre-treatment (Study Day 1), at the end of treatment (Study Days 6-9), and post-treatment (Study Days 28-32). At the end of treatment, 91 out of 114 evaluable patients (80%) had clinical cures with clarithromycin, while 71 out of 105 evaluable patients (68%) had clinical cures with amoxycillin (p = 0.057). Clinical success rates were 96% for both treatments (110/114, clarithromycin; 101/105 amoxycillin). Adverse events related to the study medications occurred in four of 132 patients receiving clarithromycin (3%) and eight out of 127 subjects receiving amoxycillin (6%). Three patients discontinued treatment due to adverse events, all three receiving amoxycillin. At the doses administered, clarithromycin given twice-daily was as safe and effective as given three-times-daily in the treatment of acute otitis media in pediatric patients.