Objective: The aim of this study was to compare cutaneous microvascular function in young healthy subjects (n=50) with that of cardiometabolic diseased patients (n=50) using laser speckle contrast imaging (LSCI) coupled with transdermal iontophoretic delivery of acetylcholine (ACh) and post-occlusive reactive hyperemia (PORH). Methods: Cutaneous blood flow was assessed in the forearm using LSCI at rest, during PORH and during iontophoresis of ACh with increasing anodal currents of 30, 60, 90, 120, 150 and 180 μA during 10-second intervals spaced 1 min apart. Results: Endothelium-dependent skin microvascular vasodilator responses induced by both ACh and PORH were significantly reduced in cardiometabolic diseased patients compared to healthy subjects. Vasodilator responses induced by ACh were significantly higher in young women than in young men. Iontophoresis charges up to 1.5 mC do not induce nonspecific effects on skin microvascular flux. Conclusion: LSCI appears to be a promising noninvasive technique for evaluating systemic microvascular endothelial function.2030-01-01