Despite several published methods of inducing surgical anesthesia in guinea pigs, viable methods of anesthesia for blood collection from the vena cava are inadequate. We compared 5 anesthesia regimens and their efficacy in inducing anesthesia for blood sampling in guinea pigs: ketamine-xylazine (30 and 2.5 mg/kg) administered subcutaneously, intramuscularly, or intraperitoneally; pentobarbital (37 mg/kg) administered intraperitoneally; and medetomidine (0.5 mg/kg) administered intramuscularly. Parameters measured included time to onset of anesthesia, time to recovery from anesthesia, and complete blood count (CBC) and serum chemistry values. CBC values did not differ among the 5 regimens, but serum glucose, BUN, phosphorous, and creatine phosphokinase levels varied among groups. Based on our data, intraperitoneal ketamine-xylazine appears to emerge as a preferable injectable anesthetic regimen in guinea pigs for blood collection from the anterior vena cava.