The Platelet Function Analyzer (PFA-100) is increasingly being used in the workup of patients with a bleeding diathesis. A profound knowledge of the possible diagnostic performance of this test is essential in order to make sound clinical decisions based on its results. It was the aim of this study to systematically review the published literature and provide valid estimates of the diagnostic performance of the PFA-100 for detecting disorders of primary haemostasis in newly presenting patients with a bleeding diathesis. A comprehensive literature search was performed for studies published between January 1994 and February 2006. Studies were eligible for the systematic review if they provided data supposed to be applicable to the determination of the diagnostic performance of the PFA-100. Furthermore, they were included in a meta-analysis if study reporting allowed calculation of sensitivity and specificity and if study quality ensured minimized biases of these estimates for the described clinical setting. Pooled weighted sensitivity, specificity and diagnostic odds ratio were calculated applying random effects modelling and constructing summary operator characteristic curves. This was done separately for the available test modifications using either collagen/epinephrine (PFA-EPI) or collagen/adenosine-diphosphate (PFA-ADP) for platelet activation. Thirty-six articles were included in the systematic review. Six studies met our eligibility criteria for a meta-analysis. The major reason for exclusion from the meta-analysis was a case-control design. A total of 1486 and 1259 patients were included in the meta-analysis of the diagnostic performance of the PFA-EPI and PFA-ADP, respectively. Pooled weighted sensitivity and specificity of the PFA-EPI/PFA-ADP in detecting a disorder of primary haemostasis were: 82.5/66.9% (95%-confidence interval (95%-CI): 76.0-88.9%/57.9-75.9%), and 88.7/85.5% (95%-CI: 84.3-93.1%/82.0-89.1%). 83/75% of patients with a positive PFA-EPI/PFA-ADP result do have a disorder of primary haemostasis whereas 88/79% with a negative PFA-EPI/PFA-ADP result do not. The PFA-EPI appeared to have a higher sensitivity and better predictive values than the PFA-ADP in detecting disorders of primary haemostasis, although a rigorous gold standard definition for a disorder of primary haemostasis, particularly for platelet disorders, was not applied in most studies. The majority of the studies lacked important requirements for quality and reporting, precluding a more precise and definitive characterization of the clinical utility of the PFA-100. This emphasizes the need for an evidence-based critical appraisal of diagnostic studies in haemostasis research in order to promote the conducting of studies that produce clinically relevant results.