We aimed to describe the epidemiologic and microbiologic characteristics of acute otitis media (AOM) with spontaneous otorrhea in children and compare it with AOM with intact tympanic membrane in children who underwent tympanocentesis. All infants and young children aged <3 years with culture-positive AOM of < or =7 days duration diagnosed during 1999 to 2006 and in whom epidemiologic and microbiologic data were available, were analyzed. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes were considered true AOM pathogens. Multivariable regression analysis models adjusting for age, gender, ethnicity, seasonality, previous antibiotics, AOM history, tympanocentesis history, and pathogens isolated, were used. Of 12,617 AOM patients from whom a middle ear fluid was obtained, 5247 (42%) culture-positive patients were enrolled; spontaneous otorrhea was observed in 822 (15%) patients. Patients with spontaneous otorrhea were older than patients with AOM who underwent tympanocentesis (15.8 +/- 8.2 vs. 9.7 +/- 6.7 months, respectively, P < 0.01; 36.9% vs. 69.1%, respectively, were <12 months, P < 0.01). S. pyogenes was found in a higher proportion (47/822, 5.7% vs. 44/4425, 1%, P < 0.01) and H. influenzae in a lower proportion (264/822, 32.1% vs. 1805/4425, 40.8%, P < 0.01) among patients with spontaneous otorrhea than in patients with AOM and tympanocentesis. In the multivariate model, Bedouin ethnicity (OR: 1.5, 95% CI: 1.2-1.7, P < 0.001), age (OR: 1.1, 95% CI: 1.0-1.11, P < 0.001) for each consecutive month, lack of antibiotic treatment for the 48 hours preceding diagnosis (OR: 2.1, 95% CI: 1.7-2.6, P < 0.001), > or =1 previous AOM episode (OR: 3.2, 95% CI: 2.6-4.0, P < 0.001), >1 previous tympanocentesis (OR: 1.4, 95% CI: 1.4-1.7, P = 0.001), and infection with S. pyogenes (OR: 8.2, 95% CI: 5.4-12.3, P < 0.001) were independent risk factors for AOM presenting as spontaneous otorrhea. AOM presenting as spontaneous otorrhea in patients less than 3 years of age is characterized by older age, previous repeated tympanocenteses, > or =1 previous AOM episodes, lack of recent antibiotic treatment, and infection with S. pyogene.