We studied the influence of cardiovascular(CV) risk factors, previous CV events, and co-treatments with preventive medicines, on residual platelet thromboxane(TX)B2 production in 182 patients chronically treated with enteric coated(EC)-aspirin(100mg/day). The response to aspirin was also verified by assessing arachidonic acid-induced platelet aggregation and urinary 11-dehydro-TXB2 levels. Residual serum TXB2 levels exceeded the upper limit value for an adequate aspirin response in 14% of individuals. This phenomenon was detected at 12h after dosing with aspirin. The co-administration of statins(atorvastatin, used mostly) was an independent predictor of residual serum TXB2 levels, and the percentage of patients with enhanced values was significantly lower in statin users vs. nonusers. We provide evidence in vitro that atorvastatin reduced residual TXB2 generation by increasing the extent of acetylation of platelet COX-1 by aspirin. In conclusion, the coadministration of statins may counter the mechanisms associated with reduced bioavailability of aspirin detected in some individuals with CV disease.