Background: Drug-eluting stent (DES) are widely used for percutaneous coronary intervention (PCI). However, it is largely unknown whether the impact of DES on coronary endothelial dysfunction or significant coronary artery spasm (CAS) is similar to De Novo CAS without significant coronary artery disease (CAD). Methods: A total 1938 consecutive patients (pts) underwent Ach induced CAS test by injecting incremental doses of 20, 50, 100 ug into the left coronary artery between March 2004 and April 2009. Among them, 160 pts treated with DES. We investigated the Ach provocation test results, its associated parameters and 12-month clinical outcomes between the pts with prior DES placement (DES Group, n=160pts) and the pts without significant coronary artery disease (No CAD Group, n=1192 pts). Results: The baseline clinical characteristics showed that the classic risk factors including male (68.8% vs 48.2%, p<0.01), diabetes mellitus (28.3% vs 9.1%, p<0.01), hyperlipidemia (23.8% vs 16.4%, p=0.02), hypertension (55.0% vs 40.7%, p<0.01), and smoking (49.4% vs 28.9%, p<0.01) were more common in the DES group. After Ach injection, the rate of positive provocation test result, response to lower Ach dose (A1) (9.4% vs 3.5%, p<0.01), and diffuse CAS pattern (61.9% vs 46.1&, p<0.01)were more common in DES group. Multivariate logistic analysis showed that DES itself was an independent risk factor for Ach-induced CAS (Adjusted odd ratio; 1.49, 95% confidence interval; 1.02-2.16, p=0.03). At 12 months, although the mortality and myocardial infarction (MI) were similar between the two groups, repeat PCI and major adverse cardiac events (MACE) were higher in the DES group. Further, the DES group showed higher rate of follow up angiography due to recurrent chest pain (Table). Conclusions: In our study, prior DES placement was an independent risk factor of Ach- induced significant CAS. Further, DES group showed higher incidence of Ach-induced CAS, vulnerable to Ach and more diffuse spasm. DES group showed worse clinical outcomes up to 12 months probably due to the recurrence after DES implantation.