The vascular endothelial function of smokers is known to be impaired. This study investigated whether cilostazol could improve the vasodilatory response of the brachial artery to ischemia, an indicator of endothelial function, in ten male smokers. Endothelium-dependent vasodilatation and endothelium-independent vasodilatation of the brachial artery were measured in 11 male non-smokers and 20 male smokers with matching age and weight. The results showed that the vasodilatory response to reactive hyperemia was significantly smaller in the smokers (4.8 ± 1.6%) when compared to that in the non-smokers (7.6 ± 2.5%) (p = 0.0013). However, no significant difference in the vasodilatory response to isosorbide dinitrate was observed between the two groups. In addition, there were no significant differences in serum lipid, Lp (a), or blood homocysteine between the smokers and non-smokers. When 150 mg/day of cilostazol was administered for two weeks, the vasodilatory response to reactive hyperemia significantly improved (4.2 ± 1.2% to 7.8 ± 3.5%, p = 0.0032). The increased vasodilatory response to reactive hyperemia by cilostazol was reduced after cessation of the drug (4.5 ± 1.5%). These findings suggest that cilostazol improves vascular endothelial dysfunction in smokers.