Objective: The role of aspirin in the primary prevention of cardiovascular disease in patients with diabetes is controversial. On the other hand, cilostazol is known to be effective in reducing various cardiovascular risks in diabetes. In the present study, we examined the antiplatelet activity and effects on lipid profile of aspirin and cilostazol in Korean patients with type 2 diabetes mellitus. Methods: We randomly assigned the 116 patients with type 2 diabetes and one more major cardiovascular risk factors but no evident cardiovascular disease to receive aspirin at a dose of 100 mg or cilostazol at a dose of 200 mg daily. The primary efficacy outcome was the antiplatelet effects of aspirin and cilostazol at baseline and after taking each drug for 14 days. We measured antiplatelet effects with the aspirin response units (ARU) using Verifynow system and the rate of platelet aggregation (RPA, seconds) due to collagen, epinephrine using PFA-100. Secondary outcome was the change of lipid profile after taking each drug for 14 days, in the fasting state. Results: The increase of ARU (-185 ± 66 vs. -2 ± 42, p < 0.001) and the decrease of RPA (118 ± 76 vs, 26 ± 73 sec, p < 0.001) were significantly greater with aspirin compared with cilostazol after 14 days. In cilostazol group, there was no significant change of ARU and RPA after 14 days. The prevalence of aspirin resistance was 7.5% by ARU ≥ 550, and 18.9% by RPA < 192s. Compared with aspirin, cilostazol treatment was associated with increased HDL cholesterol (3.5 ± 6.2, p = 0.065) and decreased triglyceride (19.3 ± 47.2 vs. 0.6 ± 78 mg/dL, p = 0.139), but statically not significant. Conclusion: After 14 days of treatment, in the present study, aspirin showed better antiplatelet effects with Verifynow and PFA-100 system compared to cilostazol. However, there were favorable changes in triglyceride and HDL cholesterol only in cilostazol treatment group.