Background: Stroke risk is increased among HIV-infected persons on stable antiretroviral therapy (ART). Inflammatory cytokines and/or endothelial activation factors caused by HIV or other factors may confer risk beyond traditional cardiovascular (CVD) risk factors. Carotid intima-media thickness (cIMT) is associated with increased stroke risk. We assessed the hypothesis that soluble plasma inflammatory and endothelial activation biomarkers would be associated with cIMT independent of the Framingham Risk Score Category (FRSC), low: <10%, medium: 10-20%, high: >20% 10 year risk of CVD. Methods: Cross-sectional analyses were done in HIV+ subjects age > 40 years on > 6 months stable ART, without prevalent CVD. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. CVD risk factors were collected and FRSC calculated. Plasma biomarkers were assayed by multiplex bead immunoanalysis. cIMT was log transformed to account for data non-normality. Univariate analyses were performed followed by sequential multivariate regression analyses for those showing significance with adjustment for age and FRSC. Results: Analyses were performed on 83 HIV+ subjects (n=72 males, median age 49 years, median CD4 Nadir 140, 72 with HIV RNA < 50, 51 with low FRSC, 12 medium FRSC , 20 high FRSC). In univariate analyses, there were significant associations between the following biomarkers and log cIMT: sVCAM-1, CRP, SAA, IL-6, IL-8, and VEGF. There were no significant associations observed for sE-selectin, sICAM-1, MMP-9, MPO, tPAI-1, SAP, IL-1b, IL-10, TNF-α, MCP1, IFN-γ, and NT-proBNP. When age and FRSC were included in the model for biomarkers showing univariate significance, log CRP ( β=0.025; p=0.02), log SAA ( β=0.028; p=0.01), log IL-8 ( β=0.083; p=0.05), and VEGF ( β=0.0004; p=0.02) remained significantly associated with cIMT. Conclusions: In conclusion, the pro-inflammatory markers CRP, SAA, IL-8 and vascular activation marker, VEGF are associated with cIMT independent of age and traditional CVD risk factors in HIV-infected subjects on stable ART and suggest that inflammation and endothelial activation pathways involving these biomarkers may in part contribute to the excess stroke risk in HIV.