Objective Aspirin has been used extensively in primary and secondary prevention of cardiovascular disease, particularly for subjects at high risk such as metabolic syndrome. However, the responsiveness to aspirin treatment may vary among individuals. The present study was conducted to investigate the profile and prevalence of aspirin resistance in patients with metabolic syndrome. Methods In 221 consecutive patients, platelet aggregation induced by arachidonic acid (0.5mg/ml) was assessed after 10 days of aspirin treatment (200mg/d). Aspirin resistance was defined as mean optical platelet aggregation =20%. Results Aspirin resistance occurred in 39 patients (17.6%). Serum fibrinogen level was higher in patients with than in those without aspirin resistance (2.6±0.4g/l vs 2.4±0.4g/L, P=0.017). The 2 groups, aspirin resistance group and no aspirin resistance group, did not differ significantly, with regard to gender, age, body mass index, waist-hip ratio, blood pressure level, serum cholesterol level and history of myocardial or cerebral infarction. Multivariate logistic regression analysis revealed that only serum fibrinogen level entered the model (odds ratio 2.973, p=0.023). Subgroup analysis further showed that aspirin resistance occurred more in male patients with myocardial infarction (50% vs14.5%, P=0.02) and in female patients with diastolic blood pressure=85mmHg (34% vs 15.5%, P=0.043). But after multifactor logistic regression, in women blood pressure=85mmHg was not a predictor any more. Conclusions In patients with metabolic syndrome, aspirin resistance is not uncommon, especially for men with history of myocardial infarction. Patients with aspirin resistance have an increased serum fibrinogen level.