This study was conducted to compare C. difficile population in commercial swine with those causing C. difficile associated diarrhea (CDAD) cases in humans. Fecal samples were collected from sows (eight per fam1) and piglets (30 per fam1) in eight farms in North Carolina (n=5) and Ohio (n=3) representing a total of 68 sows and 251 piglets. In addition, 33 C. difficile isolates were collected from CDAD cases in humans from the NC region. C. difficile isolates were tested for their susceptibility to a panel of six antimicrobials. PCR was used to detect genes coding for enterotoxin A (tcdA), cytotoxin B (tcdB) and the binary toxin (COT). We detected significantly higher piglet prevalence in Ohio (87.5%) than North Carolina (64%) (P < 0.001).