In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K channels, BK channels, and at least partly, K channels. In addition, not only the inhibition of extracellular Ca influx, but regulation of the intracellular Ca release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.