OBJECTIVE: To characterize patterns of antiretroviral use in HIV-infected patients and explore variation by patient characteristics and disease stage. METHODS: Three large patient databases recording information derived from routine clinical attendance were analyzed: HIV Insight (n = 10 873), Target Management Services (n = 2226) and Clinical Partners (n = 1505). Each database records the dates of starting and stopping individual antiretroviral agents over time, measurements of CD4 T-cell counts and HIV-RNA levels at approximately 6-monthly intervals, and the demographic characteristics of patients. The number, frequency and duration of different antiretroviral combinations over time and their relationship to stage of HIV-disease and demographic characteristics were explored. RESULTS: Over 2000 different combinations of antiretroviral agents are recorded. From 1987 onwards, the use of zidovudine increased, with 23% of patients receiving monotherapy by 1990. The majority of treated patients remained on monotherapy until the introduction of highly active antiretroviral therapy (HAART) in 1996. By 1999, the standard of care was HAART, with 84% of patients beginning antiretroviral therapy with HAART. Those of African American race (odds ratio 0.59) and funded by Medicaid (odds ratio 0.72) were significantly less likely to begin antiretroviral therapy on HAART. Until 1995, there was a significant decrease in CD4 T-cell count when starting antiretroviral therapy. No significant trend was observed in either CD4 T-cell count or viral load after this time. Those starting on HAART therapies were significantly less likely to stop or switch regimens than those on nucleoside reverse transcriptase inhibitor (NRTI)-only therapies (P < 0.001). CONCLUSIONS: Complex patterns of antiretroviral treatment are observed in this large population. Changes over time mirror the introduction of the new antiretroviral agents.