Objectives: Aspirin is recommended for primary prevention in patients with metabolic syndrome (MetS). In this study, we evaluated aspirin resistance in MetS patients. Study design: The study included 32 patients (23 males, 9 females; mean age 60.7 +/- 11.4 years) with the diagnosis of MetS, according to the criteria of the International Diabetes Federation. Aspirin resistance was determined by the PFA-100 analysis (Platelet Function Analyzer). The results were compared with a control group of 30 patients (16 males, 14 females; mean age 61.6 +/- 7.3 years) without MetS. All the patients were taking aspirin at the time of the PFA-100 analysis. Results: Overall, 21 patients (33.9%) were aspirin nonresponders. The prevalence of aspirin resistance was 46.9% in the MetS group, and 20% in the control group. The difference between the two groups was statistically significant (p=0.033). Compared to aspirin responders, fasting blood glucose level was higher (102.0 +/- 14.6 mg/dl vs. 95.3 +/- 9.9 mg/dl; p=0.036) and waist circumference tended to be greater in nonresponders (97.4 +/- 14.1 cm vs. 89.7 +/- 15.0 cm; p=0.053). Multivariate logistic regression analysis showed that MetS (OR 0.28, 95% CI 0.090.88; p=0.029), fasting blood glucose (OR 0.95, 95% CI 0.91-0.99; p=0.045), uric acid (OR 0.46, 95% CI 0.280.76; p=0.002), gamma-glutamyl transferase (OR 1.04, 95% CI 1.00-1.08; p=0.043), high-sensitivity C-reactive protein (OR 1.07, 95% CI 1.01-1.12; p=0.015) levels and platelet count (OR 0.99, 95% CI 0.98-0.99; p=0.034) significantly affected aspirin resistance. Conclusion: Our results show that a significant proportion of MetS patients will not benefit from aspirin use due to high aspirin resistance.