We conducted a controlled clinical trial to determine the efficacy of single-dose intramuscular ceftriaxone for the treatment of acute otitis media. Fifty-four children aged 18 months to 6 years with clinical and tympanometric evidence of otitis media were randomized to receive either 50 mg/kg ceftriaxone or 10 days of oral cefaclor 40 mg/kg/day. Resolution of symptoms and clinical and tympanometric appearance of the tympanic membrane at follow-up visits were used to determine outcome. Thirty-one children received ceftriaxone and 23 received oral cefaclor. There were no treatment failures. There were no significant differences between groups in persistence of effusion or recurrence of acute otitis media. We conclude that a single intramuscular dose of ceftriaxone compares favorably with 10 days of oral cefaclor for the treatment of acute otitis media.