Background The safety and advantages of CO 2 laser myringotomy for otitis media with effusion (OME) are well described. The goal of such treatment is to avoid unnecessary ventilation tube insertion. Comparisons between different age groups treated with this modality are lacking, and prognostic factors for treatment outcomes are not available. Methods We conducted a retrospective cohort study that included 130 children (160 ears) and 96 adults (108 ears) with OME persisting after conservative antibiotic treatment. In eligible patients, we performed laser myringotomy in the affected ear. Follow-up was scheduled every week for 1 month and then every month for 6 months. Results for 233 ears were available for analysis; 24 ears were excluded (19 due to cancer, four due to a cleft palate, and one due to Down syndrome) and 10 patients (11 ears) were lost during follow-up. A logistic regression model was used for analysis, with success of therapy as the binary outcome. Results Adult patients had more unilateral lesions ( p < 0.001) and serous fluid effusions ( p < 0.001) than did the pediatric patients. However, there was no significant difference in the cure rate (children: 58.1%; adults: 64.7%) and positive culture rate (children: 15.1%; adults: 14.3%) between patient groups. Three factors were found to be associated with a poor prognosis: multiple occurrences in children ( p < 0.001), mucoid effusion ( p = 0.04), and a history of ventilation tube use in adults ( p < 0.001). No other variables predicted treatment outcome. Conclusion Our findings suggest that CO 2 laser myringotomy is a useful treatment modality for OME in children and adults, except for children with multiple occurrences and in adults with mucoid effusions and a history of ventilation tube use.