We sought to assess the relationships between platelet reactivity at different time points, CYP2C19*2 and ABCB1 status and clinical outcomes in patients with acute coronary syndromes (ACS). Anti-platelet response to clopidogrel was studied prospectively using the VerifyNow (VN) P2Y12 assay at the time of angiography and at 30 days post procedure in 151 patients admitted with ACS who underwent percutaneous coronary intervention (PCI). Troponin T levels were measured at angiography and 16-24 hour following PCI. DNA was extracted and the presence of CYP2C19*2 allele and ABCB1 polymorphisms were determined. Adverse cardiovascular and cerebral events (ACCE) were assessed at 12 months. High VN P2Y12 response at angiography was associated with a greater peri-procedural rise in troponin T, but not ACCE. However, VN P2Y12 response measured at 30 days was associated with ACCE (p = 0.017). CYP2C19*2 status was associated with higher VN P2Y12 response at angiography (p < 0.0001) and 30 days (p = 0.006) but not ACCE. Near-patient testing for clopidogrel response was associated with subsequent ACCE when performed 30 days following PCI, but not at angiography.