Recurrent hepatitis C is a frequent complication after liver transplantation for hepatitis C virus– related cirrhosis, but risk factors related to its development remain ill defined. Twenty-three patients receiving a primary liver graft for hepatitis C virus–related cirrhosis and with an assessable biopsy performed at least 6 months after liver transplantation were studied retrospectively. The end point of this study was to look for risk factors associated with the development of histologic hepatitis C in the graft. Thirty-six major variables were studied, and those reaching significance by univariate analysis were included in a multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis C. On univariate analysis, six variables showed significant predictive value: increased immunosuppression for treatment of acute rejection; pretransplant hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months after transplantation; and mean blood trough levels of cyclosporine in the first 6 months posttransplantation. On multivariate analysis, two variables retained independent statistical significance as predictors of hepatitis C recurrence, namely receipt of antirejection therapy (P 5 .0087) and lower mean cyclosporine levels in the first 6 months after transplantation (P 5 .0134). Therefore, recurrence of hepatitis C after liver transplantation seems to be at least partially related to posttransplantation immunosuppressive therapy.