Background: Several studies showed that adenosine or nicorandil have myocardial protective effect against angioplasty-related myocardial injury. We conducted a prospective, randomized study to investigate the effect of intracoronary adenosine and nicorandil combination therapy on myocardial protection. Methods: 213 consecutive patients with stable or unstable angina who were scheduled to undergo non-urgent percutaneous coronary intervention (PCI) for de novo native coronary lesions were enrolled. Patients were randomized to group I (control saline, n=55), group II (adenosine 50 ug, n=54), group III (nicorandil 4 mg, n=54), and group IV (adenosine-nicorandil combination, n=50). Myocardial necrosis was assessed by elevations of creatine kinase MB isoform (CK-MB), tropinin I (cTnI) before PCI and 6h, 12h, 24h after PCI. Primary endpoint is incidence of myocardial necrosis (elevation of serum TnI) and secondary endpoint is mean CK-MB value and post-procedural myocardial infarction (MI). Results: No significant differences were observed among the four groups in the baseline and angiographic characteristics. No serious major adverse events related to adenosine and nicorandil were observed. There was no significant diffenence in the incidence of post-procedural myocardial necrosis between each groups (10.9 vs 14.8 vs 14.8 vs 14.0%, respectively, p=0.9). There were no significant difference in the incidence of post-procedural MI between each groups (p=0.6). By logistic regression analysis of the variables, multivessel stenting, implanted stent numbers, median stent lengths and side branch compromised showed the strongest connection with myonecrosis (p< 0.005). Conclusion: Pretreatment with intracoronary adenosin, nicorandil or combination of two drugs did not reduce the incidence of myocardial necrosis and MI after non-urgent PCI.