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To determine characteristics and risk factors for unmasking tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRIS) following initiation of combination antiretroviral therapy (cART) in HIV-infected patients, which have not yet been assessed to date.Retrospective single-center cohort study.Medical records of HIV-infected patients diagnosed with tuberculosis following cART initiation were reviewed. Cases of unmasking IRIS were identified using provisional consensus definitions. Characteristics of patients with and without unmasking TB-IRIS were compared. A case–control design was used to identify risk factors for unmasking TB-IRIS in patients initiating cART.Among 47 patients on cART at TB diagnosis, 11 experienced unmasking IRIS (23%). They had lower CD4% (9 vs. 14, P = 0.02), higher HIV-RNA load at baseline (5.2 vs. 4.0 log, P = 0.005), and a stronger CD4% increase with HIV-RNA decline after 1 month on cART (+7 vs. +3 log, P = 0.02, and −3.2 vs. −0.8 log, P = 0.005) than the 36 remaining patients without unmasking IRIS. In the case–control study, risk factors for unmasking IRIS were African country of origin (65 vs. 18%, P = 0.007), higher baseline HIV-RNA load (5.2 vs. 4.7 log, P = 0.01), stronger CD4% increase (+7 vs. +2, P = 0.0001), and HIV-RNA decline of more than 3 log after 1 month on cART (73 vs. 27%, P = 0.02).Patients with African origins, advanced HIV infection, or a strong response to cART are at greater risk of unmasking TB-IRIS.