Widely varying methods of assessing platelet aggregation have resulted in the absence of an established standard approach to assess the effects of antiplatelet drugs. The objective of this study was to compare the roles of collagen and adenosine diphosphate (ADP) in the assessment of effects of aspirin or clopidogrel on platelet aggregation. Sixty patients with documented coronary artery disease were assigned to receive aspirin alone (ASA 100 mg/d) (n=30) or aspirin-plus-clopidogrel (ASA 100 mg/d+C 75 mg/d) (n=30). Platelet aggregation assessment by the use of whole blood aggregation tests with collagen or ADP was performed in these patients and 30 age- and gender-matched normal volunteers. When compared with the control group, therapy with ASA or ASA+C resulted in significant inhibition of collagen-induced platelet aggregation (P<0.001 for each), but there was no statistically significant difference in the results between the ASA and ASA+C groups. When platelet aggregation was induced by ADP, the combined therapy with aspirin and clopidogrel decreased platelet aggregation significantly when compared with aspirin alone (P<0.001), and no significant difference in the results between the ASA and normal groups was observed. In conclusion, collagen may prove useful to study the effect of aspirin and ADP may be appropriate for assessing the inhibitory effect of clopidogrel.