| Summary: | Treatment of empyema is very challenging. The use of negative pressure wound therapy (NPWT), and NPWT with instillation and dwell time (NPWTi‐d) for wound closure have attracted attention. However, they are both limited to use after open‐window thoracostomy (OWT) performed to control infection. In some patients with poor general conditions, who cannot undergo surgery, no treatment for empyema is available. Therefore, we devised a new treatment for such patients with NPWTi‐d without OWT (non‐OWT NPWTi‐d). Here we present the cases of two patients with refractory empyema after intrathoracic irrigation and drainage, who underwent non‐OWT NPWTi‐d using the fistula of the thoracic drain. Both the patients recovered. The first patient was treated for 31 days. As the empyema persisted, he underwent a repeat intrathoracic drainage after which the wound healed. The second patient was treated for 20 days. Non‐OWT NPWTi‐d may be a new option to treat empyema.
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