Background: People with HIV (PWH) are at risk of developing HIV-related comorbidities, such as cardiovascular disease (CVD), which appears independent of combination antiretroviral therapy (cART). Angiopoietin (ANG) has been associated with vascular augmentation (i.e., arterial stiffness) in response to both human immunodeficiency virus (HIV) and alcohol use, but their combined health effects are not well understood. Methods: This study assessed data from the WiseApp study, examining ANG-1/ANG-2 blood serum levels and alcohol consumption in 109 adults with HIV at baseline. Alcohol consumption was measured using the Alcohol Use Disorders Identification Test - Concise (AUDIT-C) measure, and ANG-1 and ANG-2 levels were measured using high sensitivity Enzyme-Linked Immunoassay (ELISA) kits. Generalized linear mixed model analysis was used to explore the effect of alcohol consumption on angiopoietin levels in PWH, adjusting for demographic variables. Results: Alcohol consumption was not significantly associated with either ANG-1 or ANG-2 serum levels in our sample. However, CD4 serum levels were significantly correlated with both ANG-1 and 2, with a positive association for ANG-1 and negative associations for ANG-2. Additionally, demographic factors, including gender identity, sexual identity, and race, were significantly associated with ANG-2 levels but not ANG-1 levels. Conclusion: These findings underscore the complex interplay between immune function, vascular regulation, and demographic characteristics in persons with HIV. Future research should explore these relationships in larger and more diverse cohorts, incorporating longitudinal analyses to better understand the temporal dynamics of alcohol use, immune status, and endothelial function.