Introduction The incidence of pulmonary nontuberculous mycobacterial (NTM) infections has increased in recent decades. But NTM empyema is still a rare disease. The purpose of this study was to clarify the clinical characteristics and outcomes of NTM empyema. Methods The medical records of 484 patients with pulmonary NTM disease (NTM empyema 15, NTM disease without empyema 469) and 367 patients with acute empyema (NTM empyema 15, other empyema 352) were retrospectively reviewed and investigated patients with empyema with other causes as well as patients with NTM empyema from January 2012 to December 2024 in our hospital. NTM empyema was defined as a positive NTM culture of pleural effusion samples and had purulent pleural effusion. Results Among patients with pulmonary NTM and patients with acute empyema in our study, 15 had NTM empyema (3.1%, 4.1%). Age (median 78 vs. 68, p=0.0072), male (60.0% vs. 32.4%, p=0.0256), Charlson Comorbidity Index (CCI, median 6 vs. 4, p=0.0007) and fibrocavitary form patients (60.0% vs. 21.5%, p=0.0005) were higher in the NTM empyema than in the NTM disease without empyema. Although the same long-term follow-up as NTM disease without empyema was performed, the long-term prognosis of NTM empyema was poorer than that of NTM disease without empyema. Ten out of 15 patients with NTM empyema and 52 out of 352 patients with other empyema patients were complicated with pneumothorax. Compared to patients with other empyema, patients with NTM empyema had higher incidences of pneumothorax (66.7% vs. 14.8%, p=0.00002). Surgical treatments were performed for 11 patients of 15 NTM empyema - two patients died (18.2%) - and were more frequently performed for other empyema. There were significant differences between the mortality rate for fistulous patients with NTM empyema and those for fistulous patients with other empyema (40.0% vs. 11.5%, p=0.0250). All patients with NTM empyema who died had pneumothorax. No fistulous patient with NTM empyema was cured without surgical treatment. Conclusions NTM empyema patients had higher rates of fibrocavitary form, were male, and had higher CCI, and the long-term prognosis of NTM empyema was poorer than that of NTM disease without empyema. In addition, this study revealed that NTM empyema has a poor prognosis and is difficult to treat without chest tube drainage or surgical treatment. Early surgical intervention should be considered for patients with fistulous NTM empyema.