Unresponsiveness to clopidogrel or aspirin has been reported in patients with acute coronary syndrome (ACS). Platelet aggregometry (PA) and the Impact-R [Cone and Plate(let) Analyzer (CPA) technology, measuring whole blood platelet adhesion under flow conditions] were compared in detecting laboratory unresponsiveness to clopidogrel and aspirin among ACS patients. Platelet-rich plasma (PRP) samples were evaluated in 404 patients by PA using adenosine diphosphate (ADP) and arachidonic acid (AA) and whole blood samples by the Impact-R ADP- and AA-response tests. The first cohort (n=114) was assayed by PA on days 1 and 4 of the onset of ACS. A patient with relative decrease of </=10% in ADP-induced maximal platelet aggregation after clopidogrel treatment was defined as laboratory non-responding (NR) patient to clopidogrel. This relative value correlated well with an absolute value of ADP-induced aggregation >/=70%. A patient with an absolute value of AA-induced maximal aggregation >/=60% was defined as laboratory NR patient to aspirin. The second cohort (n=290) was tested on day 4 by both systems and results analyzed by receiver operating characteristic curve. The following cut-off values of the Impact-R surface coverage were obtained: </=2.8% and </=3.4% for clopidogrel and aspirin NR patients, respectively. The incidence of NR patients to clopidogrel and aspirin, according to the two methods was 27% and 22%, respectively. Impact-R compared to PA in detecting clopidogrel and aspirin NR patients revealed: 79% and 82% agreement, 71% and 73% sensitivity, 83% and 86% specificity, respectively. In conclusion, the Impact-R and PA results demonstrated high degree of similarity.