Background: Cigarette smoking may increase platelet aggregation and cause atherothrombotic cardiovascular events. We aimed to investigate the impact of cigarette smoking on platelet function in patients with ischemic coronary heart disease (CHD). Methods: Twenty patients with ischemic stable CHD under aspirin therapy (300 mg/d), who continue to smoking despite all warnings, and 20 nonsmokers with CHD are enrolled in the study. Platelet function is studied at the morning, before and 15 minutes after the first cigarette, by the Platelet Function Analyzer (PFA)-100, with collagen and epinephrine and collagen and adenosine diphosphate cartridges. Post aspirin platelet hyperactivity is defined as having a closure time (CT) shorter than 186 seconds despite regular aspirin intake. Serial CT measurements are analyzed by paired samples t test. Results: Persistent platelet activity was present in 4 smoker (20%) and 3 nonsmoker (15%) patients at the beginning. Platelet activity measured by the PFA-100 is been increased significantly after cigarette smoking (P = .004). Shorter CTs were determined after smoking in all patients with and without baseline persistent platelet activity, and 4 more participants became aspirin nonresponder (P = .004). No significant differences in demographic, hematological, and biochemical parameters were determined between aspirin responders and nonresponders. Conclusions: We determined that cigarette smoking may increase platelet aggregation in patients with ischemic CHD in an aspirin nonresponsive manner. Our results emphasize the importance of quitting cigarette smoking in patients with CHD.