Mortality in HIV-positive persons is increasingly due to non-HIV-related medical comorbidities. There are limited data on the prevalence and patient awareness of these comorbid conditions. Two hundred subjects at an urban HIV clinic were interviewed in 2005 to assess their awareness of 15 non-HIV-related medical comorbidities, defined as medical problems that are neither AIDS-defining by standard definitions, nor a direct effect of immune deficiency. Medical charts were subsequently reviewed to establish prevalence and concordance between self-report and chart documentation. Eighty-four percent of subjects self-reported at least 1 of 15 medical comorbidities and 92% had at least 1 condition chart-documented. The top 5 chart-documented conditions were hepatitis C (51.5%), pulmonary disease (28.5%), high blood pressure (27%), high cholesterol (24.5%), and obesity (22.5%). In multivariate analysis, higher number of non-HIV-related medical comorbidities was associated with older age, female gender, and intravenous drug use as route of HIV transmission. Across self-reported non-HIV-related medical comorbidities, the absolute concordance rate ranged from 67% to 96%, the sensitivity ranged from 0% to 79%; the positive predictive value ranged from 0% to 100%. While the vast majority of largely urban minority HIV-positive subjects were diagnosed with non-HIV-related medical comorbidities, there is significant room for improvement in patient awareness. In order to help patients optimally access and adhere to medication and medical care for these non-HIV-related medical comorbidities, interventions and educational campaigns to improve patient awareness that take cultural background, literacy, and educational level into account should be developed, implemented, and evaluated.