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Objectives. This study examined the prospective effect of reported access to medical care on health-related quality-of-life outcomes in patients with symptomatic human immunodeficiency virus (HIV) disease. Methods. A cohort study was designed with interviews at baseline, follow-up interviews at 3 months after baseline, mortality follow-up through 6 months after baseline, and medical record reviews for selected baseline clinical data. Participants were HIV-infected patients who were receiving ambulatory and/or hospital care at one county-run municipal and one Veterans Administration hospital in metropolitan Los Angeles and were interviewed about access to medical care (using a reliable 9-item scale assessing affordability, availability, and convenience of medical care). Access to care reported by this sample was compared with that of 2,471 patients with other chronic diseases from the Medical Outcomes Study. The main outcome measures were composite scores for physical and mental health-related quality of life 3 months after baseline, derived from a validated 56-item instrument, scored from 0 to 100, and controlling for baseline health-related quality of life. Results. Overall reported access to medical care in this sample was significantly poorer than that for patients with other chronic diseases (means scores were 63 and 73, respectively). The sample was categorized into tertiles of initial physical and mental health-related quality of life and into groups with initial high versus low access to care. Among those in the middle tertile of physical health-related quality of life at baseline, those with high access improved in physical health scores by 10.2 points relative to those with low access. Those in the low and middle tertiles of initial mental health improved in mental health to a significantly greater extent for those with high versus low access. There were nonsignificant trends toward similar effects for most other subgroups. The effects of access on health-related quality-of-life outcomes were generally robust in multivariate regression analyses that included CD4, hemoglobin, albumin, insurance status, and sociodemographic characteristics. Conclusions. Access to care at baseline predicted better physical and mental health outcomes at 3 months for those in the middle tertile of physical health and for those in the bottom and middle tertiles of mental health at baseline. Increasing access to care for poor public hospital patients with HIV infection may help to improve health-related quality-of-life outcomes among selected persons with advanced disease.