Insufficient inhibition of platelet function by acetyl salicylic acid (ASA) or other platelet inhibitors is a risk factor for arterial thrombosis in cardiovascular patients. We wanted to collect and analyse information on the frequency and probable causes of non-response to ASA in patients prior to and after cardiac surgery. One hundred and one patients (mean age 68 ± 9 years) undergoing cardiac surgery (98 patients with coronary bypass grafting, 18 cases had combined valve replacement, and three patients with only valve replacement) were enrolled. Post-operatively all patients received metamizole for analgesia. Platelet aggregation in platelet-rich plasma was induced by arachidonic acid (AA; 1.6 mM) or ADP (3 mM) in the absence and presence of exogenous ASA (100 µM). ASA non-response was defined as a maximum AA-induced aggregation of >30%. Eighty eight patients had pre-operative medication with ASA (100 mg/d), and ASA non-response was found in 24%. Irrespective of whether or not ASA medication was continued immediately after surgery, incidence of non-response increased to 55% at the first post-operative day. During continuous post-operative ASA medication (100 mg/d), 65% of patients were non-responder at fifth-7th post-operative day. When estimated on the basis of exogenously added ASA, non-response was observed pre-operative in 10%, at first post-operative day in 53% and at fifth-7th post-operative day in 39% of the patients. Twenty six of the 52 patients who did not adequately respond to exogenous ASA at the first post-operative day became responders when tested at the fifth-7th post-operative day, and 13 of the 46 responders became non-responders. The conversions were not due to small changes around the threshold of 30% aggregation but due to a highly significant decrease or increase in the extend of aggregation. Neither extracorporal circulation nor co-medication with clopidogrel had any significant influence on the platelet response to ASA medication or exogenously added ASA. Some non-steroidal analgesics, including metamizole, have been suggested to prevent inhibition of platelet cylcooxygenase by ASA. However, in 10 healthy volunteers we did not observe any interference of metamizole with the response to ASA. In conclusion, platelet response to ASA is markedly decreased after cardiac surgery. The underlying mechanisms and the clinical consequences of the post-operative instability of non-response to ASA need further evaluation.