Immune reconstitution inflammatory syndrome (IRIS) is a clinical entity with a broad presentation that is complicated in patients with acquired immunodeficiency syndrome after initiating antiretroviral therapy. A 51-year-old Japanese man was diagnosed with disseminated Mycobacterium avium complex (MAC) infection presenting as unmasking IRIS, which formed a large abscess in the patient’s abdominal wall. MAC-IRIS commonly involves the lymph nodes, bone marrow, and gastrointestinal tract. To our knowledge, this is the first case report of an abdominal wall abscess caused by MAC-IRIS.