We present a case of Mycobacterium avium-intracellulare (MAI) infection of the ankle joint in a patient with HIV infection. The patient presented with a painful, destructive arthropathy of the ankle. Initial microbiological studies were negative but infection with MAI was later identified from biopsies taken during hindfoot fusion. Antibiotic triple therapy was given and the patient remains pain-free without evidence of active infection. To our knowledge, this is the first case of MAI infection of the ankle reported in the literature. A high index of suspicion of (atypical) Mycobacterial infection should be maintained in patients with HIV infection presenting with an indolent but destructive arthropathy of the ankle joint.