Objective: To determine whether prophylactic, short-term penicillin V treatment during upper respiratory tract infections can prevent the occurrence of recurrent acute otitis media in young children. Methods: Seventy children were studied in a prospective, double-blind, placebo-controlled study. All children had suffered their first episode of acute otitis media before the age of 6 months. After inclusion in the study group, administration of penicillin V or placebo was initiated by the parents at subsequent upper respiratory tract infections. The children were examined by otomicroscopy within 3 days after treatment was initiated. The children were scheduled for a total follow-up period of 12 months, including bimonthly visits for check-up irrespective of treatment periods. Results: There were 304 treated episodes of upper respiratory tract infection. There was no significant difference in the number of acute otitis episodes between groups. Conclusion: Initiation of penicillin V prophylaxis at upper respiratory tract infection in small children did not prevent recurrent acute otitis media in this study.