CASES: Two patients with human immunodeficiency virus (HIV) developed wrist pain following the initiation of antiretroviral treatment, and were diagnosed with chronic atypical mycobacterial septic arthritis. Aggressive operative debridement led to clinical improvement, provided tissue samples for diagnosis, and allowed for a targeted long-term antibacterial regimen. CONCLUSION: Clinicians should consider atypical mycobacterial organisms as a cause of joint infection in patients with HIV. Symptoms may become apparent after patients experience immune system recovery following antiretroviral treatment.