Persistent high on-treatment platelet reactivity in acute coronary syndrome (ACS) patients managed with appropriate antiplatelet therapy has been correlated with increased risk of cardiovascular events; however, the evolution of this phenomenon overtime is not well known. We investigated platelet activity at a three month follow-up after initial presentation with an ACS. We enrolled a total of 124 patients in the study, 65 were diagnosed with ACS and 59 controls who presented with non-cardiac chest pain for baseline comparisons. Of the enrolled patients, we had 25 ACS patients return, in stable condition, three months after their initial presentation for repeat platelet functional testing. Epinephrine (EPI), adenosine diphosphate (ADP), and arachidonic acid induced platelet aggregation were monitored at baseline with repeat measurement of EPI- and ADP-stimulated aggregation at follow-up. In addition, P-selectin and PAC-1 expression were monitored at presentation and at a three month follow-up period. ACS patients were maintained on aspirin therapy during the intervening period. At the three month follow-up visit, ACS patients initiated on aspirin had no significant percentage change in aggregation to submaximal concentrations of EPI and ADP. They also had no significant percentage change in PAC-1 or P-selectin expression. This study demonstrates persistent high on-treatment platelet reactivity in ACS patients at a three month follow-up, which may place these patients at increased risk of recurrent cardiovascular events.