Statins confer an antiplatelet effect in hypercholesterolemic subjects and in stable coronary artery disease patients. We explored the antiplatelet effects of statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. Of 120 STEMI patients, 80 (67%) received statins while 40 (33%) did not. Ex vivo platelet reactivity was studied on admission and 72 hours later by conventional aggregometry and under flow conditions (Impact R). Measures of platelet reactivity under flow conditions included aggregate size and surface coverage, signifying platelet aggregation and adhesion respectively. The effect of statins on platelet function under flow conditions and platelet aggregation was studied in?vitro in platelets from 10 STEMI patients. Platelets from each patient were incubated in?vitro with lovastatin or PBS as a control. The effect of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was also studied. Patients treated with statins were compared with those who did not have significantly lower ADP-induced platelet aggregation on the 4th day (56 ± 18% vs. 64 ± 17%, p=0.02). Platelet deposition under flow conditions as measured by surface coverage was reduced from admission to 72 hours later among statin-treated patients (19 ± 28% reduction, p<0.01), but was unchanged in non-treated patients (for comparison p<0.01). The extent of platelet inhibition was unrelated to patient characteristics, including lipid profile and type of statin administered (lipophylic vs. hydrophilic). In the in vitro study platelet incubation with statin compared with PBS resulted in a lower aggregate-size (29 ± 9 μm(2) vs. 39 ± 15 μm(2), p<0.01), and lower surface coverage (8.5 ± 4% vs. 12 ± 4%, p<0.01). The effect of the statin on both parameters was significantly blunted by L-NMMA. Incubation with statin also resulted in a reduction in collagen-induced platelet aggregation (31 ± 20% vs. 54 ± 25%, p<0.01). We concluded that in acute myocardial infarction patients, statins have an early antiplatelet effect, in addition to that afforded by standard antiplatelet therapy.