Objectives The assessment of systemic microvascular reactivity is currently considered to be critical in the stratification of cardiovascular risk. In the present study, we compared skin microvascular function in individuals with early-onset (premature) coronary artery disease (EOCAD, n= 30) with that of age-matched and sex-matched healthy individuals (n =30). Materials and methods Using laser speckle contrast imaging, cutaneous blood flow was assessed in the forearm at rest and during reactivity tests, including postocclusive reactive hyperemia and the iontophoresis of acetylcholine or sodium nitroprusside with increasing currents of 30, 60, 90, 120, 150, and 180 lA for 10-s intervals spaced 1 min apart. Carotid intima–media thickness was evaluated using an ultrasound system and a 7.5MHz ultrasound transducer. Results The endothelium-dependent skin microvascular vasodilator responses that were induced by both acetylcholine and postocclusive reactive hyperemia were significantly reduced in patients with EOCAD compared with healthy individuals. The vasodilator responses that were induced by sodium nitroprusside were also significantly reduced in individuals with EOCAD. These systemic microvascular alterations were concurrent with increased carotid intima–media thickness in these patients. Conclusion Laser speckle contrast imaging identifies endothelial-dependent and endothelial-independent microvascular dysfunction in individuals presenting with EOCAD, and thus could be valuable as an early peripheral marker of atherothrombotic disease.