OBJECTIVE To assess the relative antiaggregatory ability of aspirin on platelets of smoking and nonsmoking healthy volunteers. METHODS Prospective, randomized, crossover study. METHODS Tertiary-care teaching institution. METHODS Eighteen healthy smoking and nonsmoking male volunteers. METHODS Each subject received aspirin 325 mg or ticlopidine 250 mg bid as an active control for 7 days in a crossover manner separated by a 1-month washout period. Whole blood platelet aggregation was measured on four occasions, twice at baseline and once after each drug treatment. METHODS Whole blood ex vivo platelet aggregation in terms of impedance (omega) and adenosine triphosphate (ATP) release (nmol), as assessed using Lumi-aggregometry. RESULTS Aspirin was associated with significantly less ATP release in both smokers (p = 0.01) and nonsmokers (p = 0.003). No significant differences in platelet aggregation were found between smokers and nonsmokers at baseline or with any treatment phases. Sixty-seven percent and 17% of volunteers receiving ticlopidine and aspirin, respectively, reported adverse effects. CONCLUSIONS Twice-daily administration of aspirin for 7 days to healthy volunteers was well tolerated and also reduced platelet aggregation significantly regardless of smoking status.