Background: Smoking is one of well-known environmental factors causing endothelial dysfunction and plays important role in the atherosclerosis. We investigated and compared the effects of cilostazol and sarpogrelateon the endothelial dysfunction in active male smokers with flow-mediated dilatation (FMD). Patients and Methods: We enrolled 20 male smokers without any known cardiovascular diseases. After measurement of baseline FMD, the 10 participantswere medicated with oral cilostazol 100 mg bid for two weeks. The follow-up FMD was rechecked at that time. After discontinuation of cilostazol for one week, sarpogrelate 100mg po bid were given for two weeks. The other 10 participants were medicated sarpogrelate first and switched to sarpogrelate, later. We reevaluated the follow up FMDs after two weeks and compared these values between two groups. Results: There was no statistical difference of baseline characteristics between two groups. Two of the participants, initially medicated with cilostazol, were dropped out due to severe headache after medication. Baseline endothelium dependent dilatation (EDD) after reactive hyperemia was 7.5짹 1.9% and endothelium-independent dilatation (EID) after sublingual administration of nitroglycerin 13.3짹3.4%. After two-week treatment of cilostazol, follow-up EDD was significantly increased (7.7 짹 1.9% to 8.8 짹 2.0%, p=0.016). However, follow-up EID was not significantly increased (13.2 짹 3.5% to 12.5 짹 3.9%, p=0.350). With sarpogrelate treatment, the follow-up EDD was significantly increased (7.4 짹 1.9% to 8.8 짹 1.9%, p=0.021). However, follow-up EID was not significantly increased (13.5 짹 3.5% to 14.0 짹 3.2%, p=0.427). There was no clinical significance between two groups in EDD and EID (p=0.984 and 0.212, respectively). However, the mean score of intensity of headache (VAS) significantly higher in the cilostazol group than in the sarpogrelate group (3.8 짹 2.5% vs. 1.4 짹 2.2%, p=0.005). Conclusion: The EDD was significantly increased with two-week treatment of cilostazol and sarpogrelate similarly. However, the intensity of headache was significantly higher in the cilostazol group.