The objective of this study was to evaluate the association between previous hepatitis C virus (HCV) infection and the occurrence of posttransplant diabetes mellitus (PTDM) among patients undergoing kidney transplants using tacrolimus (FK). From August 1999 to January 2003, 66 patients (36.4 +/- 15.5 years) underwent kidney transplantation using an immunosuppressive regimen of tacrolimus, mycophenolate mofetil, or azathioprine and steroids. Thirty-four patients (52%) received kidneys from living donors and 32 (48%) from cadaveric donors. The diagnosis of diabetes mellitus was established after two consecutive ambulatory measurements of fasting glycemia > or = 126 mg/dL. Thirty-five percent of the patients (23/66) were HCV+ and 65% (43/66) HCV-. Of the 66 patients, 33% (22) developed PTDM, 19 (82%) from the HCV+ group and only 3 (7%) from the HCV- group. Among those who developed PDTM, the diagnosis was established in the first 2 posttransplant months in most cases (68.2%). The results showed a significant association between HCV and PTDM (P < or = .0001). In this group of patients HCV infection was strongly associated with the development of PTDM. Therefore, additional care is required regarding the immunosuppressive regimen among patients with chronic HCV infection.