Background: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome, yet its pathophysiology is only partially understood. We sought to assess the association between endothelial dysfunction (ED) and SCAD. Methods: We prospectively assessed patients presenting with acute coronary syndrome who were diagnosed with SCAD. The control arm had established coronary artery atherosclerotic disease (AD) according to previous coronary angiography. ED was assessed using the EndoPAT 2000 while patients returned to their steady state condition. A total of 16 patients with SCAD and 66 patients with AD were included. Results: Microvascular reactivity as assessed with the EndoPAT was significantly worse in the AD group compared to the SCAD group. The median RHI in the AD group was 1.76 (IQR 1.52, 2.2) vs. a median RHI of 2.08 (IQR 1.73, 2.79) in the SCAD group (p < 0.05). While the RHI values in half of the AD group (33 patients; 50%) were below the cut-off of 1.67 only one patient had an RHI below this cut-off in the SCAD group. Conclusions: Patients with SCAD were not found to have ED and it is therefore unlikely that ED takes part in SCAD formation. (C) 2020 Elsevier Inc. All rights reserved.