AbstractBackground: The protective effect of acetylsalicylic acid (aspirin) in primary and secondary prophylaxis of cardiovascular events is attributed to the inhibition of platelet cyclooxygenase (COX). However, a recent animal study found a vasodilating and blood pressure lowering effect of aspirin independent of COX, but mediated by inhibition of the RhoA/Rho kinase signaling pathway. Method: Prospective, randomized, double-blind, placebo-controlled cross-over study. In each instance 5 healthy volunteers received either aspirin 500 mg/d or placebo for 7 days. Capillary red blood cell velocity (vRBC) at rest and after postischemic hyperemia was determined on day 1 and 7 by means of nailfold capillary microscopy. Results: In the aspirin group after 7 days a significant increase of vRBC was found at rest and during hyperemia. In the placebo group vRBC did not change. The finding was confirmed by the cross-over design of the study. Conclusion: Aspirin at a dosage of 500 mg/d has an impact on vasoregulation in the microcirculation. At present, the underlying mode of action in humans is unknown.