Aspirin, compared with placebo, reduces the risk of cardiovascular events by 25% in populations of patients with and without known arterial vascular disease. However, the phenomena of 'aspirin resistance' that has been described in 5'--50% of this population may critically reduce aspirin's efficacy. One study has suggested that aspirin-resistant patients have a 3.5 times higher risk of cardiovascular death. Presently, there are no established, simple, broadly used methods determining antiplatelet properties of aspirin, while conventional aggregometry requires special equipment and trained personnel. We sought to determine the validity of an Ultegra analyzer with the novel aspirin-sensitive cartridge before and after one pill of non-enteric coated aspirin (325 mg) in subjects with multiple risk factors for coronary artery disease. One hundred and fifty-four volunteers were enrolled into the multicenter study, but six of them were excluded. Data from 148 participants were analyzed. Platelets were assessed twice at baseline (pre-aspirin), and after 2-30 h (post-aspirin). We employed 5 micromol/l epinephrine-induced conventional aggregometry, and aspirin response units stimulated by propyl gallate with the point-of-care Ultegra analyzer. A single pill of aspirin reduced platelet-rich plasma aggregation from 72 +/- 21% to 25 +/- 10%, and diminished aspirin reduction units from 647 +/- 95 to 436 +/- 69. The overall agreement between the two methods was 87% with 85% sensitivity for Ultegra and 88% for platelet aggregation, respectively. The correlation between the two methods was 0.902. Timely determination of aspirin resistance represents an indispensable application in current medicine. The Ultegra RPFA-ASA analyzer is a novel, fast method that could be used in clinical practice for monitoring efficacy of aspirin, and for triaging the aspirin-resistant population. The clinical implications of these data need to be proven in randomized trials.