The main objective of this study was to compare testing for aspirin response in healthy volunteers by two high shear methods in a randomized double blind placebo controlled study. Seventeen healthy male individuals were randomized for aspirin 160 mg per day for 7-10 days, and 20 age matched controls for placebo for the same period. At study entry and 7-10 days thereafter we determined high shear-induced platelet adhesion to polystyrene after pre-incubation with arachidonic acid using the Cone and Plate(let) analyzer (Impact-R), and the closure time of collagen/epinephrine cartridges obtained by the PFA-100 (CEPI-CT). Platelet adhesion to polystyrene after preincubation with arachidonic acid was median 3.7% (range 0.6-8.0) before study entry and median 6.7% (range 2.8-11.0) after 7-10 days of aspirin (p < 0.001). Changes were not significant in the placebo group. By the PFA-100 CEPI-CT was median 211 s (range 130-300 s) before aspirin, and 300 s in all individuals taking aspirin for 7-10 days (p < 0.001). Post-treatment data obtained by the Impact-R and PFA-100 were discordant in seven cases from the placebo group, and in one subject on aspirin. The response to aspirin varied considerably among healthy individuals, but both methods were suitable to demonstrate the aspirin effect. There was, however, a significant level of absent concordance between the tests. Since the trial design cannot provide data on the specificity of the different tests, only clinical experience can determine their usefulness.