With improvements in surgical technique and the advent of new and more effective immunosuppressive agents, survival rates in liver transplant recipients have dramatically improved. However, hyperlipidemia frequently develops in patients administered cyclosporine-based immunosuppression long-term, although it appears to occur less often with newer, tacrolimus-based regimens. We sought to determine whether an isolated change in the baseline immunosuppressive regimen (cyclosporine to tacrolimus) would improve hyperlipidemic states in these patients. Twenty-one long-term stable liver transplant recipients with hyperlipidemia, manifested by elevated cholesterol and/or triglyceride levels, were offered conversion to tacrolimus from cyclosporine A therapy. Lipid profiles were monitored at baseline (while on cyclosporine therapy) and at 1 and 3 months after conversion to tacrolimus therapy. There were no other medication manipulations. After conversion to tacrolimus therapy, mean cholesterol levels decreased from 251 to 202 mg/dL at 1 month (P <.001) and 194 mg/dL at 3 months (P <.001). Similarly, triglyceride levels decreased from 300 to 207 mg/dL by 1 month (P =.011) and 203 mg/dL by 3 months (P <.001). There was also a statistically significant decrease for very low-density lipoprotein levels at 3 months (P =.005) and low-density lipoprotein levels at 1 and 3 months (P =.013 and P =.014, respectively). High-density lipoprotein levels did not significantly change after conversion to tacrolimus therapy. Conversion was not accompanied by adverse side effects, and patients tolerated the change well. In conclusion, simple conversion from cyclosporine to tacrolimus-based immunosuppression therapy is safe and improves posttransplantation hyperlipidemia in a subgroup of liver transplant recipients.