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Background: Controversy exists over the pattern of lipidemic effects from calcineurin inhibitors and prednisone. We report an extensive longitudinal study of lipid profiles in pediatric thoracic transplant recipients., Methods: Serial fasting lipids of subjects from a single pediatric center, along with their immunosuppressive regimens, were examined. Groups were analyzed according to cyclosporine- or tacrolimus-based immunosuppression in addition to whether prednisone was used as adjunctive therapy., Results: Of a total of 119 subjects, 85 were and remained on tacrolimus (TAC), 13 remained on cyclosporine (CSA), 4 switched from TAC to CSA, and 17 switched from CSA to TAC. The median age at transplant was 100 months, and the latest follow-up was 48 months. The CSA Group had higher lipid levels than the TAC Group, and levels changed minimally over time. At 1 year, TAC vs CSA total cholesterol was 153 vs 186 mg/dl (p = 0.002), low-density lipoprotein (LDL) cholesterol was 92 vs 117 (p = 0.09), and high-density lipoprotein (HDL) cholesterol was 42 vs 48 (p = NS), respectively. At the latest follow-up, the TAC vs CSA cholesterol was 143 vs 180 mg/dl (p = 0.001), LDL was 84 vs 115 (p = 0.001), and HDL was 42 vs 41 (p = NS). Profiles of subjects that switched agents reflected the agent used (e.g., higher total cholesterol, LDL, and HDL while on cyclosporine). Sub-group analysis showed prednisone augmented the hyperlipidemic effects., Conclusion: Hyperlipidemia is common in pediatric thoracic transplant patients and persists over time. It is more pronounced in cyclosporine subjects and is further elevated with prednisone. These findings indicate the need for close monitoring, and consideration for intervention, especially in high-risk sub-groups.