Veterinary diagnostic laboratories recover E. coli strains from sick piglets (with and without other pathogens) that do not encode for commonly encountered fimbrial adhesins but do contain genes for enterotoxins or shiga toxin. Currently the role of these strains in post weaning diarrhea and edema disease is unknown. The objectives of this study were to – 1) determine if fimbriae-negative E. coli adhere to epithelial cells; and 2) determine if these strains cause disease in weaned piglets. We examined the adherence of 29 fimbriae-negative E. coli strains to human and porcine epithelial cells. The majority of the strains, 23/29, adhered to the porcine cell line and the pattern of adherence was phenotypically distinct from F18-positive strains. Two of the fimbriae-negative strains were inoculated into 3 week-old piglets. Neither of these isolates caused overt clinical signs of postweaning diarrhea or edema disease even thought both strains encoded the edema disease toxin on their genome. These data suggest that fimbriae-negative E. coli strains are not pathogenic for weaned pigs even if they encode toxins normally associated with postweaning diarrhea or edema disease.