Coronary artery ectasia (CAE) is associated with coronary artery disease (CAD). The underlying pathophysiology of CAE is not fully understood. α1-antitrypsin (A1AT) plays a role in the tissue protease system, and AAT-1 deficiency (A1ATD) has been shown to be related to CAD. We compared A1AT serum levels in patients with and without CAE to determine the association between A1AT levels and the extent of ectasia using the Markis score. We included 50 patients (38 males) with isolated CAE and 46 patients (28 males) with normal coronary arteries after coronary angiography. The levels of A1AT were measured by nephelometry. The median A1AT levels were lower in patients with isolated CAE than in the control group (1.27 ng/mL [range: 1.07-1.37 ng/mL] vs 1.43 ng/mL [range: 1.27-1.59 ng/mL]; P < .001). According to the Markis classification, the extent of CAE was not correlated with A1AT levels ( P = .41). Our results demonstrate an inverse relationship between serum A1AT levels and CAE. α1-antitrypsin is fundamental for the stability and integrity of the arterial wall. Lack of elastase inhibition in cases of A1ATD may contribute to ectasia formation by facilitating proteolysis and weakening the arterial wall.