Acute otitis media (AOM) is a common disease in childhood. If predictors of outcome in AOM were known, it would be possible to individualize therapy. Our aim was to identify factors that predict the outcome in AOM. We enrolled 368 children with AOM (ages, 10 to 86 months). The severity of symptoms and the severity of tympanic membrane changes were graded with a scoring system. Nasopharyngeal colonization with middle ear pathogens was determined on day 1. Three outcomes were assessed: persistence of symptoms at day 5, persistence of tympanic membrane changes at day 28, and recurrence of acute symptoms prior to day 28. Persistence of symptoms at day 5 was associated with younger age (35 versus 44 months; p < .001), higher symptom score on day 1 (3.5 versus 2.9; p < .05), and colonization with Streptococcus pneumoniae (61% versus 41%; p < .05). Persistence of tympanic membrane changes at day 28 was associated with younger age (39 versus 45 months; p < .01), higher tympanic membrane score on day 1 (4.1 versus 3.6; p < .01), and nasopharyngeal colonization with S. pneumoniae, especially drug-resistant S. pneumoniae (33% versus 13%; p < .05). Recurrence of acute symptoms prior to day 28 occurred in 14% of the children. Streptococcus pneumoniae was the only pathogen associated with an increased recurrence rate (23%) as compared to the group without pathogens (7%; p < .05). Age, severity of disease at presentation, and nasopharyngeal colonization patterns were proven to be important determinants of outcome in AOM.