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Background and Purpose— Abnormalities of dermal connective tissue have been detected in patients with spontaneous cervical artery dissections (sCAD), suggesting an underlying structural defect of the arterial wall. α1-Antitrypsin (A1-AT) is a circulating serine proteinase inhibitor of proteolytic enzymes that helps to maintain the integrity of elastic and collagen fibers.Methods— To test the hypothesis that moderate deficiency of A1-AT may be a risk factor for sCAD, 22 cases with sCAD and 113 controls were included in the study.Results— Patients with sCAD had significantly mean lower levels of A1-AT compared with controls (116.0±24.9 versus 141.1±31.7 mg/dL; P<0.01). Low levels of A1-AT (<90 mg/dL) were more frequently observed in patients with sCAD compared with controls (27.3% versus 2.7%; P<0.001). A positive correlation between age and plasma levels of A1-AT was found (r=0.22; P<0.01). A1-AT levels were not affected by sex or vascular risk factors, including smoking habit. On multivariate analysis, A1-AT <90 mg/dL was associated with sCAD independently of age, sex, or vascular risk factors (odds ratio, 17.7; 95% confidence interval, 2.9 to 105.6).Conclusions— Low plasma levels of A1-AT may be a risk factor for sCAD.