This study was conducted to better understand the prognostic factors influencing the disease progression and mortality in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in a high-middle-income country. This registry-based retrospective cohort study was conducted in Tehran from April 2004 to March 2014. We enrolled 2473 HIV-infected patients who had a medical record in Behavioral Diseases Counseling Centers. The outcomes of interest were the estimation of time: (1) from HIV diagnosis to AIDS progression and (2) from AIDS to AIDS-related death. The 1-year, 5-year, and 10-year probability of disease progression from HIV diagnosis to AIDS was 45.0%, 69.9%, and 90.4%, and that of AIDS-related death was 17.2%, 30.3%, and 39.2%, respectively. Multivariate Cox regression analysis indicated that AIDS progression was significantly associated with male sex (P = 0.022), an increase in age (P = 0.001), low educational levels (P = 0.001), and a decreased level of CD4 cell count (P = 0.001). Furthermore, the AIDS-related mortality was significantly associated with male sex (P = 0.010), tuberculosis coinfection (P = 0.001), and antiretroviral therapy (P = 0.001). The results of this study indicated that progression to AIDS and AIDS-related death is affected by several modifiable and non-modifiable predictors. We indicated that a substantial proportion of the HIV-positive people were unaware of their status and were diagnosed very late. This hidden source of HIV infection had the opportunity to transmit the infection to other people.