We hypothesized that heightened systemic inflammation contributes to the increased rate of cardiovascular events in HIV-infected patients not receiving combination antiretroviral therapy. We performed a pilot trial to assess the effects of the nuclear factor-κB inhibitor salsalate on flow-mediated dilation of the brachial artery, a measure of endothelial function. Flow-mediated dilation significantly improved after 8 weeks of salsalate. However, hepatotoxicity occurred frequently. Research using alternative agents is warranted to examine the role of inflammation in HIV-related cardiovascular disease.