Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed in patients having undergone liver transplantation (LTx). These alterations are probably multifactorial in origin, and cluster to generate a metabolic syndrome (MS), increasing the risk of cardiovascular events. We assessed the prevalence of MS (National Cholesterol Education Program-Adult Treatment Panel III criteria) in 296 LTx patients in the course of regular follow-up, at least 6 months after transplantation (median, 38 months). Several pre-LTx and post-LTx data were collected to identify the factors associated with the presence of MS. In a subset of 99 patients, insulin resistance was measured by the homeostasis model assessment. High blood pressure was present in 53% of cases, hyperlipidemia in 51%, high glucose in 37%, and enlarged waist circumference in 32%. Overall, MS (defined as 3 or more of the above features) was present in 44.5% of cases. Insulin resistance (homeostasis model assessment ΟΎ 2.7) was observed in 41% of cases. Hypertension and hyperlipidemia were more frequent in subjects on cyclosporine than in tacrolimus-treated cases, whereas the type of immunosuppressive drug had no effect on the prevalence of diabetes, enlarged waist, and MS. In a logistic regression analysis, only pre-LTx body mass index (odds ratio, 1.20), body mass index increase (odds ratio, 1.18), and pre-LTx diabetes (odds ratio, 2.36) predicted MS; age, gender, etiology of liver disease, time from LTx, type of immunosuppressive drug, and previous hepatocellular carcinoma were removed from the model. Disorders related to MS are frequent in LTx patients, and are related to both pre-LTx conditions and to weight gain. Weight control is mandatory in LTx patients to prevent risk factors of premature atherosclerosis.