To investigate the effect of two clopidogrel pretreatment duration on platelet activation in patients undergoing stenting. From July 2006 to December 2007 40 elective carotid or vertebral artery stenting patients were assigned into two groups: Group A (n = 24) initiated clopidogrel (75 mg/d) > or = 5 d before stenting; group B (n = 16) initiated 3 - 4 days. Platelet-monocyte aggregates and fibrinogen receptors analyzed by flow cytometric, and platelet aggregation tests using optical aggregometry, as well as serum soluble CD40 ligand quantified by enzyme-linked immunosorbent assay were assessed in peripheral blood samples obtained immediately before and at 0.5, 18 h and 6 d after stenting. Platelet-monocyte aggregates, fibrinogen receptors and serum soluble CD40 ligand were higher in group B than in group A (14.59% vs 8.70%, P = 0.012; 4.87% vs 2.42%, P = 0.024; 5.79 microg/L vs 2.64 microg/L, P = 0.020) at 18 h after stenting. Serum soluble CD40 ligand was higher in group B than in group A (0.49 microg/L vs 0.31 microg/L, P = 0.033) at 0.5 h after stenting. Premedication before stenting with clopidogrel 75 mg/d merely 3 - 4 d may be insufficient to achieve adequate platelet inhibition, whereas clopidogrel initiated at least 5 d could obtain preferable clinical antiplatelet efficacy.