Clostridium difficile remains the leading cause of health care–associated infectious diarrhea, and its incidence and severity are increasing in liver transplant recipients. Several known risk factors for C difficile infection (CDI) are inherently associated with liver transplantation, such as severe underlying illness, immunosuppression, abdominal surgery, and broad-spectrum antibiotic use. We conducted a single-center retrospective case control study to characterize risk factors for CDI among patients who received a liver transplant from January 2008 to December 2012. We also examined the associations of post-transplantation CDI with transplant outcomes. Cases were defined as having diarrhea with a positive test for C difficile by either toxin A/B enzyme immunoassay (EIA) or glutamate dehydrogenase EIA and polymerase chain reaction within 1 year after transplantation. Sixty-five consecutive patients were evaluated, of which 15 (23%) developed CDI. The median time from transplantation to CDI diagnosis was 65 days (interquartile range [IQR] 13–208) and more than one-half (53%) had severe infection. Risk factors that were associated with CDI among liver transplant recipients included: (1) previous history of CDI (20% vs 0%; P = .001); (2) exposure to proton-pump inhibitor therapy (93% vs 60%; P = .015); (3) antimicrobial therapy before transplantation (47% vs 18%; P = .039); (4) a prolonged length of stay before transplantation (1 day [IQR, 1–19] vs 1 day [IQR, 0–1]; P = .028); and (5) chronic kidney disease (53% vs 20%; P = .011). There was no significant differences in patient survivals at 6 months (93% vs 96%; P = .67) and 12 months (87% vs 94%; P = .35) among CDI case and control subjects, respectively.