Antiplatelet therapy with aspirin (ASA) is widely used in cardiovascular disease (CVD) prevention because it inhibits platelet cyclooxygenase-1 (COX-1) and thromboxane A2 (TXA2)-mediated platelet aggregation, but not everyone fully benefit from ASA due to incomplete TXA2 suppression. Among the mechanisms to explain ASA failure (poor ASA response or ASA resistance), oxidative stress and inflammation have emerged as relevant factors. The relationship of urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive stable metabolite of TxA2, and oxidative stress (urinary 8-isoPGF2α) in a cohort of stable coronary artery disease (CAD) patients on ASA treatment with the risk of adverse outcomes (mortality) was investigated. In this session, the effect of aspirin on platelet cyclooxygenase COX-1 and thromboxane (TxA2) inhibition, and its use in cardiovascular disease prevention will be reviewed. This review will include current laboratory measurement of urinary 11dhTxB2, a stable inactive metabolite of TxA2, to assess ASA response as a risk factor of CVD including mortality. Study results confirmed that laboratory measurement of urinary 11dhTxB2 represents a strong independent risk factor for all-cause mortality among stable CAD patients on ASA therapy. These results also indicate that 8-isoPGF2α and COX-2 thromboxane production not affected by ASA may maintain platelet hyperactivity irrespective of COX-1 inhibition. Poor ASA inhibition of 11dhTxB2 (ASA resistance) may prompt additional anti-oxidative and/or anti-inflammatory therapy in these patients aimed at modifying 5-year mortality risk.