Cardiac allograft vasculopathy (CAV) is the main cause of graft failure and death 1 year after heart transplantation (HTx). Metabolic syndrome (MS) increases the risk of cardiovascular events by endothelial dysfunction. The purpose of this study was to determine if patients with MS developed a higher risk of CAV 1 year after HTx. Since January 2004 until April 2009, 155 HTx patients were recruited. Cardiopulmonary transplants were excluded (12 patients), as well as retransplants (5 patients), pediatric transplants (11 patients), patients who refused to participate (3 patients), and those who died during the first year (35 patients). The final analysis included 89 patients. MS was diagnosed when Adult Treatment Panel III modified and revised criteria were met, before HTx or after the first 3 months. CAV was diagnosed through intravascular ultrasound performed 1 month and 1 year after HTx. CAV was defined as an intimal thickening ≥ 0.5 mm in the follow-up with regard to the one of the basal study. Development of CAV was significantly higher in patients with MS (59% vs. 19%, P<0.0001). Patients with more criteria of MS had a higher development of CAV: no criteria (4%); one criterion (4%); two criteria (47%); three criteria (62%); four criteria (75%); and five criteria (100%). Variables related to CAV in a multivariate analysis were MS (odds ratio [OR] 7.97; 95% confidence interval [CI]: 2.77-22.96; P<0.001), donor's age (OR 1.07; 95% CI: 1.01-1.13; P=0.019), low high-density lipoprotein cholesterol (OR 0.26; 95% CI: 0.09-0.71; P=0.009), and hypertriglyceridemia (OR 4.08; 95% CI: 1.45-11.50; P=0.008). Presence of MS distinguishes a subgroup of patients with high risk of developing CAV. Narrow and personalized monitoring of these patients would be recommendable.