Salmonella infection in swine prior to slaughter is a significant risk factor to pork quality, with the eventual possibility of food borne illness in consumers. Since most cases of human salmonellosis result from ingestion of contaminated food products of animal origin, numerous efforts have been made to resolve this problem. Transmission of Salmonella prior to slaughter seems to be uncontrollable by available commercial means. The purpose of this study is to evaluate the feasibility of using bacteriophage (phage) to reduce the levels of Salmonella in acutely infected pigs, in order to ultimately provide new means to control the amount of contaminated pork that may be intended for consumption. To accomplish this goal, FO-1 phage was selected for this study due to its ability to lyse a broad range of Salmonella enterica serovars. Using several experimental designs, the FO-1 phage was applied to Salmonella infected pigs and evaluated for efficacy. Administration of F0-1 phage consistently reduced Salmonella level through all of the animal trials in the present study. In all cases, the degree of reduction was between 1.0 and 4.0 logs, despite differing conditions. Considerable numbers of Salmonella remained in the intestinal contents of phage-treated pigs, indicating the possible limitations of phage therapy as a practical intervention method. Nevertheless, the results presented here demonstrate that a phage-based intervention strategy could be a possible approach for reducing Salmonella levels of acutely infected pigs if its efficacy is improved. The optimal conditions for utilizing phage to reduce Salmonella in swine should be ascertained by determining both the efficacy of phage treatment in preventing the natural transmission of Salmonella and the minimum concentration of phage particles able to effectively reduce the levels of Salmonella in swine.