HIV protease inhibitor ritonavir (RTV) may induce vascular dysfunction through oxidative stress. Ginsenosides have been shown to have potential benefits on the cardiovascular system through diverse mechanisms including antioxidative property. The objective of this study was to determine whether ginsenosides could prevent coronary arteries from RTV-induced dysfunction. Porcine coronary artery rings were incubated with RTV and ginsenosides Rb1, Rc and Re for 24 h. Vasomotor function was recorded with a myograph tension system. In response to thromboxane A2 analogue U46619, the contraction of the vessel rings was significantly reduced. When co-cultured with Rb1, Rc and Re, the contractility significantly increased. In response to bradykinin at 10^-5M, the endothelium-dependent relaxation of vessel rings was significantly reduced by 59% for RTV as compared to controls (P<0.05). When co-cultured with Rb1, Rc and Re, the relaxation significantly increased for 100%, 90% and 134%, respectively, as compared to RTV alone groups (P>0.05). In response to sodium nitroprusside, RTV significantly reduced vasorelaxation. In addition, the eNOS mRNA levels were significantly reduced by 78% for RTV group (P<0.05) by real-time PCR analysis. The eNOS protein levels by western blot and nitrite concentrations by Griess assay were also decreased, while O₂^- production by lucigenin enhanced chemiluminescence was significantly increased in the RTV-treated group. These effects of RTV were effectively blocked by ginsenosides. Thus, HIV protease inhibitor RTV significantly impaired vasomotor function of porcine coronary arteries. This effect may be mediated by down-regulation of eNOS and over-production of O₂^-. Ginsenosides can effectively block RTV-induced vascular dysfunction.