The invention features methods for preventing platelet activation and aggregation and for treating individuals suffering from conditions or undergoing procedures that may result in unwanted platelet aggregation. The methods are based on the intravenous, subcutaneous, or transdermal administration of a platelet activation or aggregation inhibitor, e.g., xemilofiban, followed by oral administration of the same or a different platelet activation or aggregation inhibitor. The treatment may commence prior to a medical or surgical procedure or after the outbreak of an adverse medical condition, either of which results in the activation of platelets that may lead to thrombus formation, and may continue thereafter.