- Background: Otitis media is an important cause of pediatric consultation, and knowledge of yearly pathogen distribution might improve antimicrobial selection. Objectives: To determine the seasonal pathogen and antimicrobial resistance distribution among Costa Rican children with otitis media. Methods: Between 1999 and 2004, 952 children with otitis media, aged 3–144 months who participated in various clinical trials, were analyzed. Data obtained from this period were compared against historical data collected between 1992 and 1997. Results: Five hundred sixteen (52%) children had a baseline middle ear fluid pathogen isolated. The most common pathogens were Streptococcus pneumoniae 252 (49%), Haemophilus influenzae 190 (37%), S. pyogenes 38 (7%), and Moraxella catarrhalis 36 (7%). The overall proportion of H. influenzae (24–37%; P = 0.01) and the production of β-lactamase producing H. influenzae (2.6–7%; P = 0.02) increased from 1992–1997 to 1999–2004. There was a nonstatistically significant trend for a higher frequency of S. pneumoniae and H. influenzae isolates detected during the rainy season than during the dry season: S. pneumoniae 58% versus 42% but not significant (P = 0.1) and H. influenzae 68% versus 32% (P = 0.06), respectively. During the rainy season, penicillin-nonsusceptible S. pneumoniae was identified more frequently (38.5%) than during the dry season (18%) (P = 0.003; odds ratio: 2.94; 95% confidence interval: 1.4–6.45). Penicillin-nonsusceptible S. pneumoniae decreased from 46.5% (1999–2001) to 16% (2002–2003) and this was associated with a significant decline of a circulating 19F penicillin-resistant S. pneumoniae serotype (from 89% to 26%), respectively. Conclusions: S. pneumoniae and H. influenzae are the 2 most common pathogens producing otitis media in Costa Rican children. An increase in the number of H. influenzae and M. catarrhalis was observed in recent years. Penicillin-nonsusceptible S. pneumoniae isolates were more commonly observed during the rainy season, in which increased morbidity with respiratory pathogens is observed.