Background: The idea that peripheral artery disease (PAD) and coronary artery disease share the same pathogenesis of endothelial dysfunction has been well described. However, whether PAD is an independent risk factor of significant coronary artery spasm (CAS) is still unclear. Methods: A total 1,027 patients (pts; 93 PAD, 934 non-PAD) who underwent coronary angiography with acetylcholine (Ach) provocation test were enrolled. Ach was injected in incremental doses of 20mg (A1), 50mg (A2) and 100 mg (A3) and significant CAS was defined as transient >70% luminal narrowing. Results: Baseline characteristics were similar between the two groups. The CAS in baseline coronary angiography was significantly higher in the PAD group than that of non-PAD group. PAD group showed a higher positive spasm test rate, higher response to lower Ach dose, higher incidence of multi-vessel spasm, higher rate of chest pain, fixed lesion and myocardial bridge (Table). The EKG change, coronary spasm extent (focal or diffuse) did not differ between the two groups. The multivariate logistic analysis showed that PAD was the strongest independent risk factor of significant CAS (OR 4.978, p= 0.001). Conclusion: PAD is an independent risk factor of significant CAS. Pts with PAD showed more baseline spasm, vulnerable to Ach provocation test and multivessel spasm. Proper antianginal coverage for preventing significant CAS should be considered in pts with PAD presenting variant anginal symptoms.