This study was undertaken during the late fall, winter, and early spring months to determine the efficacy of daily trimethoprim/sulfamethoxazole (TMP/SMX) administration in the prevention of recurrent acute otitis media (RAOM) in a specific high-risk pediatric population. Twenty-one ambulatory patients, 10 in the study group and 11 in the control group, were selected from a medical university clinic and a local private practice. The study group receiving prophylactic therapy for six months suffered no recurrences, as compared with eight children suffering one recurrence each in the control group that was treated only acutely. The results were significant at p less than 0.005 with df = 1, determined by the Fischer's exact test and the chi-square method using Yates's correction factor. These data indicated that a mean dose of TMP/SMX 6.8/34 mg/kg/d divided into twice daily doses and given for six months was safe and effective in controlling RAOM infections in a high-risk pediatric population.