Technical Abstract: Mortality and morbidity associated with Escherichia coli annually cause economic losses to the swine industry. Enterotoxigenic strains of E. coli affecting nursery-age pigs have become more difficult to treat due to increased antibiotic resistance and alternatives to antibiotics are currently being sought. Our laboratory developed a defined culture of commensal bacteria of porcine GI tract origin, maintained it in continuous-flow culture for 3 years, and designated it as RPCF. Laboratory studies have shown that RPCF-treated pigs had decreased mortality and reduced bacterial shedding compared to controls when challenged with enterotoxigenic strains of E. coli. The objective of the present study was to evaluate the efficacy of RPCF to protect nursery-age pigs in commercial swine operations from field challenge by enterotoxigenic strains of E. coli. In field trials involving six geographically separated farms with a history of high mortality from K-88 and F-18 strains of E. coli, piglets were administered RPCF within 24 h of birth and were monitored throughout the nursery period. A total of 21,467 piglets were treated with RPCF while a similar number of piglets on the same farms served as untreated controls. On farms A, B, C, D, and E, mortality in RPCF-treated pigs decreased by a mean of 2.6%, compared to untreated pigs. There were no differences on the basis of treatment on Farm F. When projected to an annual basis, the costs benefits from reduced medication costs and mortality averaged $24,663 per farm. Results from the present field trials indicate that under commercial conditions, RPCF was effective in controlling disease induced by enterotoxigenic E. coli and RPCF may be a viable alternative to the use of antibiotics.