A single preoperative dose of antibiotic proved as effective as a preoperative and 7-day postoperative course in reducing complications following rumenotomy in cattle. Exploratory rumenotomy was performed on 29 healthy Angus steers, which were allotted to the following treatment groups: (1) no antibiotic therapy, (2) single-dose, preoperative, antibiotic prophylaxis, using potassium penicillin G, and (3) preoperative potassium penicillin G prophylaxis, followed by a 7-day postoperative course of procaine penicillin G. Steers receiving antibiotics had significantly greater postoperative feed intake, lower rectal temperatures, and fewer abscesses at the surgical site than those receiving no antibiotics. There was no significant difference between animals receiving a single preoperative dose of antibiotic and those treated for an additional 7 days after surgery. In human medicine, it is generally agreed that a single preoperative dose of antibiotic offers effective prophylaxis. There are few published reports on antimicrobial prophylaxis in the veterinary literature, particularly in regard to large animals. Considering USDA requirements for milk withholding times and withdrawal times prior to slaughter for food animals receiving antibiotics, the findings of this study have medical as well as economic value.