It was the aim of the present study to perform a systematic review of the published studies that estimated the prevalence of non-responders to aspirin, as assessed by the closure time of PFA-100, a point-of-care device, and to analyse: 1) some major clinical and methodological factors that can influence it and 2) its possible association with vascular outcomes. The prevalence of non-responders to aspirin in 64 populations from 53 studies, comprising 6,450 subjects, had a median value of 0.27. A higher number of aspirin non-responders was found among older patients, those with acute vascular events, or those treated for more than one month. Aspirin non-response was more frequently associated with the use of "home-established" cut-offs or when closure time was only assessed after aspirin (rather than both before and after). Among risk factors, type 2 diabetes appeared to be associated with a higher prevalence of aspirin non-responders. The latter was also higher in less recent publications and in studies that used 3.2% rather than 3.8% Na-citrate as an anticoagulant. In eight studies comprising 847 subjects, aspirin non-responders were more likely to have vascular events than responders (relative risk: 1.63; 95% CI 1.16-2.28). In conclusion, although there appears to be heterogeneity among the studies analysed, this review indicates that about one quarter of people receiving aspirin would be identified--as an average--as aspirin non-responders by PFA-100. As this is a simple, widely available point-of-care test, efforts to better standardize it and to control for its major methodological variables might be useful to improve monitoring of platelet performance under aspirin treatment and to firmly establish the observed association with clinical vascular events.