Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.