Background: Microvascular vasomotion, i.e. rhythmic changes in vascular diameter, is thought to play an important role in ensuring optimal delivery of nutrients and oxygen to tissue. Impaired microvascular vasomotion has been demonstrated in states of obesity and type 2 diabetes mellitus (T2DM) (i.e. decreased vasomotion), and hypertension (i.e. enhanced vasomotion). It is unclear however, which factors influence microvascular vasomotion. Therefore, we investigated associations between traditional risk factors and microvascular vasomotion in a healthy population. Methods: We measured skin microvascular vasomotion in 241 healthy individuals (mean age 56 ± 8 years, 42% men, mean body mass index (BMI) 25.4 ± 3.6 kg/m2) enrolled in the Maastricht Study. We selected a healthy population without T2DM, hypertension, prior cardiovascular disease, or use of cardiovascular medication. Skin blood flow was measured with a laser Doppler probe at the dorsal side of the left wrist. Fast-Fourier transform analysis was performed to determine the five frequency components to the variability of the laser Doppler signal (i.e., endothelial, 0.01-0.02 Hz; neurogenic, 0.02-0.06 Hz; myogenic, 0.06-0.15 Hz; respiratory, 0.15-0.40 Hz; and heart beat, 0.40-1.60 Hz). The associations of age, sex, waist circumference, total-to-HDL cholesterol, 24-h mean arterial pressure (MAP), fasting plasma glucose, and cigarette smoking with microvascular vasomotion was analyzed by use of multiple linear regression analysis. Results: Higher waist circumference and 24-h MAP were associated with a lower and higher total microvascular vasomotion, respectively. Per one standard deviation (SD) higher waist circumference total microvascular vasomotion was -0.17 SD (95%CI: -0.32; -0.03) lower. One SD higher 24-h MAP was independently associated with a 0.18 SD (0.04; 0.32) higher total microvascular vasomotion. We found no associations of microvascular vasomotion with age, sex, total-to-HDL cholesterol, fasting plasma glucose, or smoking. Analysis of the five frequency bands revealed that these results were largely attributable to the contributions of the endothelial, neurogenic, and myogenic components. Sub-analysis with exclusion of the obese subjects (BMI>30 kg/m2; n = 23) gave similar results. Conclusion: In conclusion, in a healthy population waist circumference is inversely associated with microvascular vasomotion. In addition, blood pressure is directly associated with microvascular vasomotion. These data suggest that both elevations in waist circumference and blood pressure may affect microvascular vasomotion, and subsequently optimal nutrients delivery and tissue perfusion.