Some ambulant people with HIV are cared for primarily by their general practitioner and some in an outpatient clinic. Costs and patterns of care in these settings were studied in 65 such patients based in Zürich, from a limited societal perspective (excluding patient costs) based on medical resource use. Antiretroviral therapy (ART), other medications and patient variables were collected prospectively, and non-medication resources (professional time and investigations) and treatment history data were collected from medical records and by record linkage to the Swiss HIV Cohort Study database. Cost differences between the settings were estimated using multiple regression, controlling for differences in case-mix. ART comprised 80% of the total cost, non-medication costs 15% and non-ART medications 5%. Total costs were higher in the outpatient clinic (estimated additional cost after controlling for case-mix = 3489 Swiss Francs per year at 1999 prices, 95% confidence interval 742 to 6236, p=0.017). The difference was accounted for by higher ART costs in the outpatient clinic, not through a tendency to use more expensive drugs or higher doses but rather through the use of more drugs concurrently. Differences in ART prescribing patterns between the doctors in the outpatient clinic and the general practitioners were considerable and appear worthy of further investigation.