Background: Although tube thoracostomy with fibrinolytic agents and video-assisted thoracoscopic (VATS) decortication are relatively equivalent in the treatment of empyema with regard to time to patient defervescence and hospital discharge, the potential for greater benefit with VATS decortication in the setting of advanced empyema has not been explored fully. This paper describes our transition from a policy of drainage and antibiotics to primary operative management with VATS. We wanted to assess the safety and efficacy of primary operative management as a first-line treatment for advanced disease. Methods: A retrospective review was conducted of 25 patients treated for stage 3 or 4 empyema. The primary endpoints were morbidity and death. The secondary endpoints were conversion to an open procedure, time to defervescence, and length of hospital stay. Results: The morbidity rate was 16% with no deaths. No patient required conversion to open decortication. The mean time to defervescence was 3.2 days, and on average, patients were discharged on postoperative day 9. Patients were discharged home earlier when managed primarily with VATS. Conclusions: Video-assisted thoracoscopic decortication is a safe and effective treatment for pediatric stage 3 or 4 empyema.