The recurrence of ischemic cerebrovascular events despite treatment with aspirin (ASA) and/or clopidogrel remains a serious problem. Although there is increasing evidence that clinical failure may at least partially result from the nonresponsiveness of platelets to medication, the adjustment of the therapy according to ex vivo platelet responses is not yet common in clinical practice. Here, we compare two commonly used ex vivo platelet function tests under different treatment conditions. Blood samples from 142 patients with cerebrovascular disease receiving either ASA, clopidogrel, or a combined treatment, and 51 controls were evaluated by the platelet function analyzer (PFA)-100 (collagen/epinephrine cartridge), as well as collagen and ADP-induced aggregometry. The tests all demonstrated the interindividual heterogeneity of platelet aggregation inhibition, but the fractions of nonresponsiveness differed considerably with 58-62% of patients being nonresponsive to ASA by PFA-100 compared with 27-33% by collagen-induced aggregation. The clopidogrel nonresponsiveness was 44% by ADP-induced aggregation. The agreement of the test values between PFA-100 and collagen-induced aggregometry was weak (correlation coefficient r= -0.1 to -0.3). Only about half of the patients were consistently identified as either ASA responsive or nonresponsive by both tests. Under dual therapy conditions, the unspecificity of aggregometric tests prevented reliable measurements of platelet responses. In conclusion, there are currently considerable limitations in platelet aggregation monitoring. Nevertheless, we encourage prospective trials to improve the predictive value of platelet aggregation testing and to prove whether a systematic strategy of "platelet aggregation-adapted treatment" will improve the clinical outcome of patients with cerebrovascular events.