Thoracic empyema can be disabling and may need microvascular free flaps in some intractable cases. After repeated failure of conventional thoracic surgical procedures, 2 patients with empyema were treated with microvascular free vastus lateralis muscle flaps for obliteration of the large empyema cavity. The reconstruction was successful in wound closure and eradication of infection. The donor site morbidity was minimal, and the patients resumed normal daily activities. Microvascular vastus lateralis muscle flap is the best option if free flaps are required for reconstruction of empyema.