Acute aerobic and resistance exercise has been shown to reduce local muscular artery stiffness in the exercised limb while having no effect on the non-exercised limb. The stimulus for these modulations may be related to local muscular compression of underlying vasculature. The purpose of this study was to examine arterial stiffness before and after a series of locally applied external mechanical compressions designed to be similar to the resistance exercise concentric/eccentric duty cycle. One rapidly inflatable cuff was placed around the upper thigh and another around the calf of the left leg in 18 healthy, young (24 +/- 1 years) participants (female n = 10). Cuffs were inflated to a supra-systolic pressure of 200 mmHg for 4 s followed by a 2-s rapid deflation period. One "set" consisted of 12 inflation/deflation cycles. Six sets of 12 compression cycles were performed. Pulse wave velocity (PWV) was used to measure central stiffness (carotid to femoral) and peripheral stiffness (femoral to dorsalis pedis of both legs) before and 10 min after mechanical compressions. No change was found in central PWV (6.2 +/- 0.3 m/s to 6.3 +/- 0.3 m/s, P > 0.05). Peripheral PWV in the non-compressed leg did not change (8.5 +/- 0.4 m/s to 8.3 +/- 0.4 m/s, P > 0.05) while peripheral PWV in the compressed leg significantly decreased from pre to 10 min post (8.6 +/- 0.3 m/s to 7.6 +/- 0.3 m/s, P < 0.05). External compression reduced local artery stiffness of the compressed limb while having no effect on arterial stiffness of the non-compressed limb or central artery stiffness.