Nontuberculous mycobacteria (NTM) disease is of increasing public health concern, data regarding pleural effusion in NTM disease patients are limited. The purpose of this study was to investigate the clinical relevance and characteristics of NTM pleuritis. Patients with pleural effusion and NTM disease diagnosed between April 2012 and November 2017 were enrolled, their medical records were retrospectively reviewed. Clinical characteristics and treatment outcomes were analyzed. Among 100 cases with NTM disease, NTM pleuritis occurred in 7 cases (7%). Flow cytometry of T and B lymphocytes revealed an varying degrees of cellular immunodeficiency in 5 cases (71.4%). NTM pleuritis occurred with pneumothorax in 5 cases (71.4%), of whom bronchopleural fistula (BPF) was found in 4. Diagnostic delays were present in all 7 patients, and the mean time was 7 months (1 months-2years). Four patients successfully completed treatment, three patients (42.8%) died due to progressing NTM disease. Low A c c e p t e d M a n u s c r i p t 3 CD4-positive T-cell counts are common in NTM pleuritis patients. Delayed diagnosis and treatment resulted in increased incidence of NTM pleurisy and poor prognosis. Moreover, perhaps BPF is a characteristic feature of Mycobacterium avium complex (MAC)-associated pleuritis.