Objectives To investigate the clinical features of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (TB-IRIS) in patients co-infected with HIV/TB or latent infection during highly active antiretroviral therapy (HAART). Methods HIV-infected patients treated in the Third People’s Hospital of Shenzhen, China between March 2012 and March 2013 were recruited, and divided into 3 groups: 1) HIV/TB co-infection group (n = 50), 2) HIV/ MTB latent infection group (n = 50), and 3) HIV infection group (n = 50), with 12-month follow-up. Patients in the HIV/TB co-infection group were treated with HAART 2 weeks after TB therapy. Patients were assessed at different time-points. Results The incidence and mortality rates of TB-IRIS were 40% and 10% in the HIV/TB co-infected patients, and 2% (and no mortality) in the HIV/MTB group. The HIV infected group did not display TB-IRIS or death. About 95% HIV/TB co-infected patients were 20-39 years old when TB-IRIS occurred, and 65% of the patients developed TB-IRIS 2 weeks after HAART. For the co-infection group, those with TB-IRIS (20/20, 100%) had fever, with a significantly higher incidence than those who did not develop TB-IRIS (6.7%, 2/30, P < 0.05). The patients with TB-IRIS in co-infection group displayed markedly higher clinical biochemical markers, acute phase reactants, increased CD4+ cell counts, and 2 log10-decreases of HIV RNA loads, compared with the patients not presenting with TB-IRIS (P < 0.05). Conclusion HIV/TB co-infected patients presented with a high-risk of developing TB-IRIS during HAART treatment. Early diagnosis and treatment could decrease mortality rates in TB-IRIS.