Background Sarpogrelate, a serotonin blocker, has been reported to inhibit the serotonin-induced proliferation of aortic smooth muscle cells. We sought to evaluate the impact of sarpogrelate on neointimal hyperplasia after drug eluting stent (DES) implantation comparing to Cilostazol, This prospective randomized and double blind, parallel-group non-inferiority study trial was designed to investigate the safety and efficacy of sarpogrelate with suggesting non-inferiority to cilostazol phosphodiesterase inhibitor widely applied for clinical use. Methods Two hundred patients who underwent elective drug eluting stent were randomly assigned to triple treatment group(sarpogrlate, aspirin, clopidogrel n = 100) or standard triple group (cliostazol, aspirin, clopidogrel n = 100). A sample size of 200 patients per treatment arm was established using a non-inferiority margin of late lumen loss 0.1 mm, as having 80% power. Follow-up coronary angiography was performed 6 months later and 12 months clinical major adverse cardiac events MACE were carried out. Results The two groups had similar baseline characteristics and angiographic characteristics with similar vasulcar complexity (high to intermediate Syntax Score sarpogrlate 15.3% vs standard 8.3% P=0.133). The quantitative coronary angiography (QCA) at 6 months follow-up showed there was no difference between two groups in late loss. Late lumen loss (LL) (sarpogrelate group (0.32짹0.20)mm vs standard group 0.30짹0.32mm; P=0.88). 12 months MACCE were equivalent in treatment groups (sarpogrelate group 7% vs standard group 10%; P=0.447). On top of that, 6 months target lesion revasularization (TLR) were similar ( 6% vs 5% P=0.88 ). Conclusion Triple therapy with sarpogrelate is an safe regimen for prevention of not only late loss but also major adverse cardiac events suggesting non-inferiority to the standard triple therapy with cilostazol.