Aspirin protects many though not all patients from acute cardiovascular events. It is generally accepted that such prophylactic effect depends mainly on the antithrombotic action involving inhibition of thromboxane A(2) production and platelet aggregation. In many patients aspirin failure to protect against cardiovascular event is obvious, as their symptoms simply cannot be controlled by the administration of a single drug. Others do not adhere properly to the treatment regimen. There is, however, a group of subjects, in which aspirin fails to inhibit platelet function (measured by various in vitro tests) and thromboxane A(2)(TxA(2)) formation (measured either in whole blood or as urinary TXA(2) metabolite excretion). There is evidence that such impairment of biochemical aspirin effect may be of importance in predicting future cardiovascular events. Several factors can influence antiplatelet effectiveness of aspirin; among them: hypercholesterolemia, increased expression of the isoform 2 of cyclooxygenase, genetic factors (polymorphisms of beta(3) integrin, and factor XIII A-subunit), use of other nonsteroidal anti-inflammatory use, and possibly others. Still, several questions remain unanswered. While biochemical aspirin resistance can predict major cardiovascular events we are still lacking a reliable test to predict such a risk in an individual patient. In addition, we do not know whether any alteration in therapy may improve clinical outcome in a subject identified as aspirin-resistant.