Background/Objectives: Lipoprotein(a), Lp(a), is an independent causal risk factor for cardiovascular disease (CVD), where levels are regulated by the apolipoprotein(a), apo(a), gene. HIV-infected individuals are at significantly elevated CVD risk compared to HIV-uninfected individuals. The role of Lp(a) in HIV-related CVD remains unclear. We investigated the association between Lp(a) level, apo(a) size polymorphism and subclinical atherosclerosis in HIV-infected and HIV-uninfected women in the Women’s Interagency HIV Study. Methods: Lp(a) level, apo(a) size polymorphism and common carotid artery intima-media thickness (cIMT) were determined in 150 HIV-infected and 100 HIV-uninfected women. Lp(a) levels were square-root transformed to achieve normality. Linear regression models were used to evaluate the association of Lp(a) with cIMT adjusting for confounders. Results: The mean ages for the HIV+ and HIV- groups were 31 ± 4 and 30 ± 4 years, respectively. The majority of women were African-Americans (69% and 76% in the HIV+ and HIV- group, respectively). HDL-cholesterol, triglyceride and Lp(a) levels were significantly lower in the HIV+ vs. HIV- group. Prevalence of atherogenic small size apo(a) (<22 Kringles) was ~20% in both groups. Notably, Lp(a) level was predictive of cIMT in the HIV+ group [β = 0.00541, 95% CI = (0.000608, 0.010212), p =0.029], but not in the HIV- group [β = 0.00175, 95% CI = (-0.0045024, 0.0080024), p =0.584]. After accounting for confounders (age, race, smoking, BMI, blood pressure, HCV co-infection, menopause, blood lipids, treatment status, CD4+ T-cell count, and HIV/RNA viral load), the association remained significant [β = 0.00532, 95% CI = (0.0000672, 0.0105728), p =0.049] in the HIV+ group. Conclusions: Lp(a) level is associated with subclinical atherosclerosis in young HIV-infected women. Further research is needed to identify mechanisms underlying Lp(a)-associated increased CVD risk in HIV-infected individuals.