Several studies indicate that a biochemically reduced response to aspirin increases the risk of cardiovascular events. This study was designed to investigate the performance of Multiplate whole blood aggregometry as regards assessment of platelet function prior to and after aspirin treatment, and to compare it with light transmission aggregometry (LTA). We included 21 healthy individuals and 43 patients with documented coronary artery disease (CAD). Platelet aggregation induced by arachidonic acid 0.5 mM was measured in duplicate by Multiplate aggregometry and LTA in healthy individuals before aspirin treatment and in all participants on four consecutive days during treatment with 75 mg aspirin daily. Optimal compliance was confirmed by complete suppression of serum thromboxane B(2) in all participants. Employing the Multiplate, the coefficient of variation (CV) was lower at baseline (CV = 8%) than during aspirin treatment in both healthy individuals (CV = 46%) and patients (CV = 46%). During aspirin treatment, the repeatability of LTA was superior to Multiplate measurements. However, the Multiplate was superior to LTA as regards the ability to discriminate platelet response before and after aspirin treatment. In conclusion, the repeatability of Multiplate aggregometry was good before aspirin treatment, whereas the CV was quite high during aspirin treatment in both healthy individuals and patients. However, the Multiplate device was fully capable of assessing platelet function prior to and after treatment with aspirin. Clinical studies are needed to investigate whether a high platelet aggregation level measured by Multiplate whole blood aggregometry during aspirin treatment is associated with a poor clinical outcome.