We previously showed a prolonged inhibition of current-induced vasodilation (CIV) after a single oral high-dose of aspirin. In this study, we tested the hypothesis of platelet involvement in CIV. Nine healthy volunteers took 75 mg aspirin/day, 98 mg of clopidogrel bisulfate/day, or placebo for 4 days. CIV was induced by two consecutive 1-min anodal current applications (0.08 mA/cm²) through deionized water with a 10-min interval. CIV was measured with laser Doppler flowmetry and expressed in percent of cutaneous vascular conductance: %C_b. In a second experiment in 10 volunteers, aspirin and placebo were given as in experiment 1 but a 26-hour delay from the last aspirin intake elapsed before acetylcholine iontophoresis and post-occlusive hyperemia were studied in parallel to CIV. In experiment 1: the mean±SEM amplitude of CIV was 822±314, 313±144 and 746±397 %C_b with placebo, aspirin (p<0.05 from placebo and clopidogrel), and clopidogrel (NS from placebo), respectively. In experiment 2: CIV impairment with aspirin was confirmed: CIV amplitudes were 300±99, and 916±528 %C_b under aspirin and placebo, respectively (p<0.05), whereas vasodilation to acetylcholine iontophoresis (322±74 and 365±104 %C_b) and peak post-occlusive hyperemia (491±137 and 661±248 %C_b) were not different between aspirin and placebo, respectively. Low dose aspirin, even 26 hours after oral administration, impairs CIV, while acetylcholine-mediated vasodilation and post-occlusive hyperemia are preserved. If platelets are involved in the neurovascular mechanism triggered by galvanic current application in humans, it is likely to occur through the cyclo-oxygenase but not the Adenosine-di-phosphate pathway.