Acetyl salicylic acid (ASA) and clopidogrel are extensively used in the prevention of cardiovascular disease. However, the responsiveness to ASA treatment may vary among individuals. This study was conducted to investigate the profile and prevalence of ASA resistance in cardiac patients. From August 2007 to August 2008, a total of 282 cardiac patients were enrolled. Two study groups were identified: patients taking 100 mg ASA daily but without clopidogrel, and patients taking both 100 mg ASA and 75 mg clopidogrel daily. Platelet function was determined with the Multiplate analyzer to determine platelet responsiveness. Salicylate blood level was measured for all patients on ASA. Seventy-three patients (26%) were determined to be nonresponsive to ASA, and 45 patients (16%) were partially responsive, whereas 164 patients (58.2%) were responsive to ASA. Myocardial infarction and coronary obstruction were both strongly associated with ASA nonresponsiveness (p < 0.001). ASA resistance occurred more in female patients (p = 0.002). The salicylate blood level was found to be low in ASA-resistant patients (35.33 ± 50.22 mg/l) and higher in sensitive patients (54.26 ± 18.7 mg/l; p < 0.001). Quantitative assessment of platelet functions is predictive of ASA treatment failure in individual patients. Dual antiplatelet treatment with clopidogrel and ASA was found to have greater inhibitory effects on platelet aggregation than either agent alone. Non-adherence may be a significant mediator of poor outcome.