The previous reports demonstrated that ginseng saponins, active ingredient of Panax ginseng, inhibited blood vessel contraction induced by various hormones or high $K^+$. Recently, we demonstrated that 20(R)- and 20(S)-ginsenoside $Rg_3$. regulate ion channel activities with differential manners. The aim of this study was to examine whether ginsenoside $Rg_3$ isomers also show differential effects on swine coronary artery contractionresponses induced by high $K^+$, serotonin (5-HT) or acetylcholine. Treatment of 20(S)- but not 20(R)-ginsenoside $Rg_3$ caused a concentration-dependent relaxation of coronary artery contracted by 25mM KCI. 20(S)- and 20(R)-ginsenoside $Rg_3$ induced significant relaxations of coronary artery contraction induced by 5-HT $(3{mu}M)$ in the presence of endothelium with concentration-dependent manner and, also in the absence of endothelium only 20(S)-ginsenoside $Rg_3$ induced a strong Inhibition of coronary artery contraction induced by 5-HT in a concentration-dependent manner. 20(S)-ginsenoside $Rg_3$ caused relaxation of coronary artery in the absence and presence of endothelium. In contrast, treatment of 20(S)- and 20(R)-ginsenoside $Rg_3;(100{mu}M)$ did not show significant inhibition of coronary artery contraction induced by acetylcholine $(0.01;to;30{mu}M)$ in the presence of endothelium, whereas both isomers caused significant inhibition of coronary artery contraction induced by acetylcholine $(0.01;to;30{mu}M)$ in the absence of endothelium in a concentration-dependent manner. These findings indicate that 20(S)-or 20(R)-ginsenoside $Rg_3$ exhibits differential relaxation eff3cts of swine coronary artery contractions caused by high $K^+$, acetylcholine, and 5-HT treatment and that this differential vasorelaxing effects of ginsenoside $Rg_3$ isomers also might be dependent on endothelium.