Background: Serotonin (5-HT) is associated with platelet aggregation. Sarpogrelate, a selective 5-HT2A receptor antagonist, may have potential as anti-platelet agent with advantage of very short half life. Anti-platelet efficacy of sarpogrelate compared with currently used anti-platelets is unknown. Methods: Total 80 participants were randomized to aspirin, clopidogrel (Group I), aspirin, clopidogrel, cilostazol (Group II), aspirin, clopidogrel, sarpogrelate (Group III), aspirin, sarpogrelate (Group IV). All participants received a single 200 mg aspirin, 300 mg clopidogrel, 200 mg cilostazol, 300 mg sarpogrelate loading dose followed by a 100 mg aspirin, 75 mg clopidogrel, 200 mg cilostazol, 300 mg sarpogrelate daily maintenance dose for 5 days according to the assigned regimen. Maximal platelet aggregation (MPA) induced by collagen 2.0 ���/ml or adenosine diphosphate (ADP) 5 關mol/l stimuli was compared using light transmittance aggregometry. The inhibition rate defined as percent difference between the pre and post treatment aggregation rate/pre treatment aggregation rate was also compared. Results: Pre treatment MPA value was similar between all groups. All post treatment MPA values was significantly lower as compared with pre treatment values in all groups after collagen or ADP stimuli (Figure). Post treatment MPA value was significantly lower in group II than group I or IV irrespective of aggregation stimuli, collagen or ADP. Post treatment MPA rate was also significantly lower in group III than group I only after collagen stimuli, not ADP stimuli. The inhibition rates were group I 58.23%, II 77.84%, III 72.02% and IV 63.31% regarding collagen. The corresponding values with ADP were 68.45%, 78.50%, 72.78% and 55.33%, respectively. Conclusion: We found that sarpogrelate have additional platelet inhibitory effect on top of current anti-platelet agents. Regarding very short half life, sarpogrelate may be used as alternative anti-platelet agents before major surgery in patients who should take anti-platelet agents.