Twenty-six female beagles were used to evaluate the effects of intravenous and long-term subcutaneous administration of cephalothin, cefazolin, and cefmetazole on platelet function and the coagulation cascade. Platelet aggregation in response to an adenosine diphosphate (ADP) agonist, bleeding time, platelet count, platelet size, prothrombin time (PT), and activated partial thromboplastin times (aPTT) were evaluated before and 90 minutes after two intravenous doses (22 mg/kg) of cephalothin, cefazolin, and cefmetazole given at 90-minute intervals. Dogs given saline injections were used as controls. Platelet count, platelet size, PT, and aPTT were evaluated after 7 days of subcutaneous administration of saline, cefazolin, and cefmetazole (22 mg/kg every 8 hours). A significant decrease in platelet aggregation in response to ADP was detected 90 minutes after intravenous administration of cephalothin. Bleeding time was increased significantly 90 minutes after intravenous administration of cefmetazole. Platelet size was decreased significantly 24 hours after onset of the study in all animals, including controls. No significant changes in platelet count, platelet size, PT, or aPTT were detected after 7 days of subcutaneous administration. Cefazolin had no adverse effects on platelet aggregation in response to ADP, bleeding time, platelet count, platelet size, PT, or aPTT. Therefore, cefazolin should be considered as a perioperative antibiotic in dogs with conditions predisposing to hemostatic complications.