The aim of this study was to predict the clinical efficacy of different antimicrobials in the treatment of patients with acute otitis media (AOM), before and after the change in the proportion of middle ear pathogens observed after the introduction of the new conjugated heptavalent penumococcal vaccine (pPCV-7). The therapeutic Outcomes model was used to predict the likelihood of clinical success. According to this mathematical model the obtained rank order of predicted clinical efficacy was similar in the pre-PVC7 period and the post-PVC period. The results suggest that ceftriaxone and amoxicillin/clavulanate are the antibiotics with the highest predicted clinical efficacy, whereas cefaclor, azithromycin, erythromycin and clarithromycin are those with the lowest predicted clinical efficacy. The differences between antibiotics with good and those with low antibacterial activity were greater when only cases of bacterial AOM were considered. Antibiotics for which the highest clinical efficacy was predicted should maximize the likelihood of cure in outpatient antibiotic treatment of AOM.