Adiponectin is secreted in mature adipocytes, has a role in diabetes and obesity and has been studied in coronary artery disease (CAD), considered cardioprotective, what is nonetheless controversial. The assessment of systemic microvascular reactivity is useful for the evaluation of cardiovascular diseases, and laser speckle contrast imaging (LSCI) is an innovative approach, using the cutaneous microcirculation as a representative vascular bed. We evaluated serum adiponectin levels in early-onset CAD (EOCAD) patients and age-matched controls, as well as their association with microvascular function assessed by LSCI. EOCAD was defined as any obstruction ≥50% on coronary angiography, prior myocardial infarction, or myocardial revascularization in patients ≤45 years. Patients with acute coronary syndromes or interventions for <6 months were not included in the study. Controls were adults ≤45 years without CAD or cardiac symptoms. After a 12-h fast, venous blood was collected. Adiponectin was measured in serum by ELISA (Human High Molecular Weight Adiponectin, Millipore, Missouri, USA). Cutaneous microvascular reactivity was evaluated using LSCI (PeriCam; Perimed, Sweden), as previously described, using transdermal iontophoretic delivery of acetylcholine (ACh) or sodium nitroprusside (NPS). Perfusion changes were measured in arbitrary perfusion units and expressed as peak values, representing the maximal vasodilation observed, and area under the curve of vasodilation. The study complied with the 1964 Declaration of Helsinki and its amendments and was approved by the local ethics committee. Informed written consent was obtained from all participants. Categorical variables were expressed as n (%) and compared with Chi-square. Continuous variables were expressed as a mean ± standard deviation or median/ interquartile range, compared with Mann–Whitney’s test. Correlations were evaluated with Spearman’s test. A value of P < 0.05 was considered statistically significant.