The HIV epidemic is a significant global health care issue. With increasing knowledge and improved therapeutics the natural history of the infection has been modified. In this paper we aim to present the general socio-demographic profile and the clinical and therapeutic spectrum of patients with HIV infection who have visited the Bayamón Health Care facilities over the last 12 years and who are part of the Retrovirus Research Center (RRC). The objectives of the study are: 1) describe changes in the demographic, risk factors and clinical stage of patients with HIV infection initially seen in our center; 2) assess changing trends from the clinical and immunological perspective across time; 3) describe mortality risk of patients particularly after the introduction of antiretroviral therapy (ART). This is a cross-sectional study of 3,569 patients admitted to the RRC at the Universidad Central del Caribe between years 1992 through 2005. The variables studied were demographic, risk factors exposure, HIV status at baseline, clinical and immunological parameters, ART and the mortality risk. Chi square with Cramer's coefficient, Kaplan Meier and Cox proportional hazard ratio analysis were performed. The study revealed that individuals presenting at our health care facilities are older and that the proportion of females has increased. The risk factor profile shows increase in heterosexual contact with the disease. The study found that patients treated with ART had significantly lower mortality risk than those without ART. Patients who arrive to RRC with AIDS and Intravenous Drug Users (IDU) had a higher mortality risk than participants with HIV. The analysis of the trends showed changes in the demographic and clinical profile of patients across the years. HIV/AIDS prevention programs and policies need to be continued in Puerto Rico in order to better control the spread of the epidemic.