Summary. Background: Aspirin ‘resistance’ is a widely used term for hyporesponsiveness to aspirin in a platelet function test. Serum thromboxane (TX) B2 is the most specific test of aspirin’s effect on platelets. Objectives: (i) To examine the role of pre-existent platelet hyperreactivity in aspirin ‘resistance’. (ii) To determine the correlation between aspirin resistance defined by serum TXB2 and other assays of platelet function. Methods: To enable pre-aspirin samples to be drawn, platelet function was measured in normal subjects (n = 165) before and after aspirin 81 mg daily for seven days. Results: The proportion of the post-aspirin platelet function predicted by the pre-aspirin platelet function was 28.3 ± 7.5% (mean ± asymptotic standard error) for serum TXB2, 39.3 ± 6.8% for urinary 11-dehydro TXB2, 4.4 ± 7.7% for arachidonic acid-induced platelet aggregation, 40.4 ± 7.1% for adenosine diphosphate-induced platelet aggregation, 26.3 ± 9.2% for the VerifyNow Aspirin Assay®, and 45.0 ± 10.9% for the TEG® PlateletMapping™ System with arachidonic acid. There was poor agreement between aspirin-resistant subjects identified by serum TXB2 vs. aspirin-resistant subjects identified by the other five assays, irrespective of whether the analysis was based on categorical or continuous variables. Platelet count correlated with pre-aspirin serum TXB2 and VerifyNow Aspirin Assay, but not with any post-aspirin platelet function test. Conclusions: (i) Aspirin ‘resistance’ (i.e. hyporesponsiveness to aspirin in a laboratory test) is in part unrelated to aspirin but is the result of underlying platelet hyperreactivity prior to the institution of aspirin therapy. (ii) Aspirin resistance defined by serum TXB2 shows a poor correlation with aspirin resistance defined by other commonly used assays.