Background Periodic acceleration in the direction of the spinal axis through repetitive movement increases the shear stress on the vascular endothelium. In the present study it was assessed whether whole-body periodic acceleration with a new device would enhance endothelial function in sedentary adult volunteers. Methods and Results Twenty-six sedentary subjects (44±3 years) were randomly assigned to remain sedentary or perform exercise training for 4 weeks, followed by crossover. Periodic acceleration was applied with a horizontal motion platform at 2-3 Hz and approximately ±2.2 m/s² for 45 min. Increases in the brachial artery diameter were examined at rest, during reactive hyperemia (flow-mediated dilatation: %FMD) and after sublingual administration of 0.3 mg nitroglycerin (%NTG) using high-resolution ultrasound. All subjects completed the study with no adverse side-effects. There were no significant changes in the resting heart rate or arterial pressure, body weight, or lipid profiles during the study. Although %FMD did not change during the non-training period with periodic acceleration, it significantly increased from 7.3±0.4% at baseline to 8.4±0.4% after the training period (p<0.05), while %NTG remained unchanged. Conclusions Whole-body periodic acceleration with a horizontal motion platform improved vascular endothelial function in sedentary adults. This device might offer an alternative to active exercise for patients whose medical condition limits physical activity. (Circ J 2008; 72: 139 -143)