Objectives: HIV infection has become a manageable chronic disease as a result of treatment advances. Secondary prevention efforts have proved inadequate to reduce the estimated incidence of new HIV infections. Epidemiological data suggest that geographical clustering of new HIV infections is a common phenomenon, particularly in urban areas among populations of low socioeconomic status. This study aimed to assess the relationship between neighbourhood conditions and HIV management and engagement in high-risk behaviours. Methods: During routine out-patient HIV clinic visits, 762 individuals from the St Louis metropolitan area completed behavioural assessments in 2008. Biomedical markers were abstracted from their medical records. Multi-level analyses were conducted based on individuals' census tracts. Results: The majority of the sample were male and African American. In the adjusted models, individuals residing in neighbourhoods with higher poverty rates were more likely to have lower CD4 cell counts and be current smokers. In neighbourhoods with higher rates of unemployment, individuals were less likely to have a current antiretroviral prescription. In more racially segregated neighbourhoods, individuals reported more depressive symptoms. Conclusions: Despite the advances in HIV disease management, neighbourhood characteristics contribute to disparities in HIV care. Interventions that address neighbourhood conditions as barriers to HIV management may provide improved health outcomes. © 2013 British HIV Association.