BACKGROUND Acute otitis media (AOM) is a common and important source of morbidity in children, although most cases resolve spontaneously. While frequently recommended, decongestant and antihistamine therapy is of unclear benefit. OBJECTIVE To determine the efficacy of decongestant and antihistamine therapy in children with AOM on outcomes of AOM resolution, symptom resolution, medication side effects, and complications of AOM. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003); MEDLINE (January 1966 to December 2003), EMBASE (January 1990 to July 2003) and reference lists of articles for this updated review. We also contacted study authors and pharmaceutical companies. METHODS Randomized controlled trials evaluating decongestant or antihistamine treatment for children with AOM were included. Patient-oriented outcomes were considered most relevant. There were no quality or language restrictions. METHODS Investigators independently evaluated studies for inclusion, performed validity assessments, and completed data extraction. Dichotomous data were pooled to generate relative risks; homogeneity was assessed using approximate chi-square tests. RESULTS Fifteen trials involving 2695 people were included. Only the combined decongestant-antihistamine group demonstrated statistically lower rates of persistent AOM at the two week period (fixed relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.96; number needed to treat (NNT) 10). No benefit was found for early cure rates, symptom resolution, prevention of surgery or other complications. There was a five to eight -fold increased risk of side effects for those receiving an intervention, which reached statistical significance for all decongestant groupings. Validity sub analyses demonstrated that lower quality studies found benefit, while analysis of those studies with higher validity scores found no benefit of treatment. CONCLUSIONS Given lack of benefit and increased risk of side effects, these data do not support the use of decongestant treatment in children with AOM. There was a small statistical benefit from combination medication use but the clinical significance is minimal and study design may be biasing the results. Thus, the routine use of antihistamines for treating AOM in children cannot be recommended.