A 64-year-old neurologically asymptomatic woman with rheumatoid arthritis who was treated with the tumor necrosis factor (TNF)-α antagonist adalimumab developed disseminated tuberculosis (TB). After receiving anti-TB therapy and discontinuing adalimumab, she exhibited paradoxical worsening due to immune reconstitution inflammatory syndrome (IRIS) with the appearance of meningitis and brain tuberculomas. This case indicates that continuing anti-TNF therapy may be necessary to prevent IRIS in patients who develop TB, particularly disseminated TB, during the course of anti-TNF therapy. In addition, careful screening for central nervous system (CNS) TB should be performed prior to the initiation of therapy, as even neurologically asymptomatic patients can develop CNS manifestations of IRIS.