OBJECTIVES: Clopidogrel with aspirin is used to prevent thrombosis.  However, significant interpatient variability in platelet response to clopidogrel has been reported.  As many as 33% of patients are considered to be clopidogrel non-responders (NRs).  A recent meta-analysis has shown that clopidogrel resistance is associated with a 3.5-fold increased risk of ischemic events.  There are several platelet function assays (PFAs) available to assess clopidogrel resistance, the gold-standard being light transmission aggregometry (LTA).  Other PFAs have been developed, including vasodilator-stimulated phosphoprotein phosphorylation (VASP), and VerifyNow® (VN), the latter being a point-of-care assay.  However PFAs are not frequently used in the clinical setting since they are expensive, and time- and labour-intensive.  It is of interest to compare the reliability of various PFAs in the identification of clopidogrel NRs. METHODS: A MEDLINE search was conducted (1966-2010) using the following MeSH terms: Clopidogrel, Resistance, and Platelet Function Assay.  Patient-based studies which compared the proportion of clopidogrel NRs using different PFAs were retrieved.  RESULTS: Four studies were retrieved.  Of these studies, 3 demonstrated significant heterogeneity among PFAs in their assessment of clopidogrel responsiveness.   The proportion of clopidogrel NRs identified with the various PFAs ranged from 13%-39%, 44%-69%, 35%-90%, and 69%-70% in the 4 studies respectively. CONCLUSIONS: The ability to identify clopidogrel NRs by different PFAs varies greatly according to the assay used.  In addition, LTA and VASP are associated with poor quality control, expense and long turnaround times, and they are typically restricted to specialized laboratories in research hospitals.  The inability of current PFAs to accurately assess clopidogrel resistance may place unidentified clopidogrel NRs at increased risk of ischemic events.  The challenges and costs associated with such tests may be eliminated by newer therapies which have less response variability than clopidogrel.