The present study was designed to evaluate the usefulness of laboratory monitoring of antiplatelet therapy by means of a multiparametric evaluation of in vitro platelet aggregation tests in the attempt to individually optimize a given therapeutic regimen. The presence of a condition of hyperaggregability was shown in approximately 80% of patients with different forms of atherosclerotic vascular disease not undergoing any therapeutic regimen with antiplatelet agents. Conversely, a significant decrease in platelet activity was observed in patients undergoing different therapies based on acetylsalicylic acid (ASA), ticlopidine, or indobufen. The similar antiaggregatory effect of low-dose vs. high-dose ASA therapies was also shown. Dipyridamole alone showed no antiaggregatory effect, which, in turn, was reached only by the addition of ASA. Nevertheless, the association of ASA plus dipyridamole did not show any stronger antiplatelet effect than ASA alone. The evaluation of in vitro platelet activity in a group of patients treated with picotamide failed to show any significant change in comparison with the untreated group, probably due to the short half-life of picotamide in man and/or to its capability of reversibly antagonizing the action of thromboxane at receptor level. The evaluation of a long-term follow-up of 90 patients treated with different antiplatelet agents supports the idea that a multiparametric analysis of in vitro platelet aggregation may provide valuable help in monitoring and optimizing a given therapeutic regimen.