Background. Empyema with bronchopleural fistula often causes severe respiratory failure due to the inhalation of pus. Although bronchial occlusion is useful, it can be difficult to identify the bronchi responsible for air leakage. Case. A 58-year-old man was hospitalized with a lung abscess and bronchopleural fistula with empyema. A chest tube was placed and drained, but severe respiratory failure due to the inhalation of pus into the left lung occurred. Ventilator management and extracorporeal membrane oxygenation were introduced to maintain the blood oxygen concentration and improve pneumonia. To resolve the intractable air leakage, bronchoscopy was performed. However, there were multiple air leaks, and the responsible bronchi could not be identified. Indigo carmine was administered intrathoracically through the chest tube to identify the leaking bronchi. Repeated bronchial occlusion using an Endobronchial Watanabe Spigot reduced the air leakage. Conclusion. We believe that indigo carmine intrathoracic administration is useful for identifying the responsible bronchi in cases with multiple air leaks, and even in cases of bronchopleural fistula with severe respiratory failure, multimodality treatment may save lives.