Objective To evaluate the efficacy and safety of triple antiplatelet therapy (cilostazol combined with clopidogrel and aspirin) in senile patients undergoing multiple drug-eluting stents (DES) implantation of complex coronary lesions. Methods Totally 128 senile patients (65-75 years old) undergoing multiple DES implantation for complex coronary lesions were enrolled from March 2006 to September 2009. After percutaneous coronary intervention, the patients were randomly divided into control group (clopidogrel 75 mg/d and asprin 100mg/d, n=67) and triple antiplatelet therapy group (cilostazol 100mg twice a day for 3 months in addition to aspirin 100mg/d and clopidogrel 75mg/d, n=61). From 3 months to 12 months after the operation, all patients received 75mg/d clopidogrel. The clinical data were analyzed, including the clinical characteristics, coronary lesion, paratmeter of multiple DES implantation and major cardiovascular event (MACE) of all the patients in a follow-up period of a mean (20.4±5.1) months. Results The ratios of fatal or non-fatal myocardial infarction (MI) and target vessel revascularization (TVR) were significantly lower in triple antiplatelet therapy group than in control group (6.56% vs11.94%, P=0.043; 6.56% vs 13.43%, P=0.042). So the overall incidence of primary end point including death, MI and TVR was obviously lower in triple antiplatelet therapy group than in control group (9.84% vs 17.91%, absolute risk reduction 8.07%, P=0.043). There was no significant difference in the incidence of all-cause death between the 2 groups(1.64% vs 2.99%, P=0.615). The incidence of stent thrombosis during 30 days and follow-up period was obviously lower in triple antiplatelet therapy group than in control group (0.00% vs 2.99%, P=0.050; 1.64% vs 4.48%, P=0.048). While for secondary end points such as major and minor bleeding events, no significant difference was found between the 2 groups(1.64% vs 0.00%, P=0.343; 3.28% vs 2.98%, P=0.846). Conclusion Triple antiplatelet therapy for 3 months after PCI procedure significantly reduces the risk of adverse events and stent thrombosis in senile patients undergoing multiple DESs for complex coronary lesions and appears to be safe.