Dyslipidemia from highly active antiretroviral therapy (HAART) use has been reported to be less severe among persons with HIV and hepatitis C (HCV) compared to those with HIV monoinfection. However, the effect on lipoprotein ratios is less clear. The total cholesterol/high-density lipoprotein ratio (TC/HDL-C ratio) is a robust measure of cardiovascular disease (CVD) risk but has not been examined in the context of HIV/HCV-coinfected patients. We compared the TC/HDL-C ratio before HAART initiation and after at least 6 months on HAART between patients monoinfected with HIV and coinfected with HIV and HCV. Pre- and post-HAART TC, HDL-C, and non-HDL-C were also assessed. Although TC, HDL-C, and non-HDL-C significantly increased after HAART initiation in both HIV and HIV/HCV patients, the TC/HDL-C ratio did not. In addition, although the pre- and post-HAART TC, HDL-C, non-HDL-C, and TC/HDL-C ratio were significantly different between HIV and HIV/HCV patients, the magnitude in the change from pre- to post-HAART was not significantly different between infection groups. These results persisted after controlling for age, sex, race, current pharmacotherapy for lipoproteins, body mass index, and current CD4 cell count. The magnitude of change in the TC/HDL-C ratio after HAART initiation is not significantly different between HIV and HIV/HCV patients, suggesting subsequent CVD risk in HIV/HCV patients may be greater than currently appreciated.