Mycobacterium avium complex pulmonary disease (MAC-PD) can be serologically diagnosed according to the presence of anti-glycopeptidolipid (GPL)-core IgA antibodies. However, few studies have examined the association between serum anti-GPL-core IgA antibody titers and the clinical characteristics of patients with MAC-PD. From April 2014 to June 2019, we determined the level of anti-GPL-core IgA antibodies in 489 MAC-PD patients at our institute. Of them, 89 patients fulfilled the criteria of the American Thoracic Society and the Infectious Diseases Society of America statement on the diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. These patients were divided into antibody-positive (n = 59) or -negative (n = 30) groups according to their serum anti-GPL-core IgA antibody results. Additionally, the positive antibody group was further divided into a strong positive group (n = 27) and a weak positive group (n = 32), and their clinical characteristics were retrospectively compared. Disease progression requiring treatment during the 12 months following diagnosis and extensive radiological findings were significantly abundant in the strong positive group compared with the weak positive group. Our findings revealed that serum anti-GPL-core IgA antibody titers are useful not only for diagnosing MAC-PD but also for predicting the risk of exacerbation.