Introduction: Antiretroviral therapy (ART) is a life-saving treatment for the human immunodeficiency virus (HIV). However, the starting of ART is often complicated by immune reconstitution inflammatory syndrome (IRIS) in tuberculosis (TB). This study was done to examine the clinical profile of patients with IRIS in HIV-TB coinfection and their outcomes. Materials and methods: A prospective observational study was conducted at the Government Hospital of Thoracic Medicine, Chennai, Tamil Nadu, India, from January to December 2013. Patients diagnosed to have HIV and TB coinfection, those on anti-tuberculosis therapy (ATT) and ART, patients with paradoxical IRIS, and ART-naïve patients were included in the study. A total of 230 patients were studied and followed up for 1 year. Clinical examination and chest X-rays, sputum smear for acid-fast bacillus (AFB), baseline CD4 count, ultrasonogram of the abdomen, routine blood investigations, and other necessary parameters required to determine IRIS TB in HIV/TB coinfected patients were taken. Results: Among the 230 HIV patients studied, 74.3% were males, and the mean age was 39.01 ± 9.60 years. The incidence of IRIS was 20.9%, and the mortality rate was 25% among them. Oral candidiasis was the most common opportunistic infection (37.8%). Among IRIS patients, 62.5% had stage III clinical disease. Conclusion: The time of starting ART is critical to reducing IRIS-associated morbidity. Improved knowledge of the pathophysiology of IRIS will enable better diagnostic modalities and targeted treatments to be developed.