Objective To compare clinical, laboratory, lifestyle, and sociodemographic parameters and cardiac risk in antipsychotic-treated patients with and without metabolic syndrome (MS). Methods A multicenter cross-sectional study in which 117 psychiatrists recruited antipsychotic-treated outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorder. MS was diagnosed when 3 or more of the following criteria were met: waist circumference >102 cm (men)/>88 cm (women); serum triglycerides ≥150 mg/dl; HDL cholesterol <40 mg/dl (men)/<50 mg/dl (women); blood pressure ≥130/85 mmHg; fasting blood glucose ≥110 mg/dl. The 10-year cardiovascular (CV) risk was assessed by the Systematic COronary Risk Evaluation (SCORE) function (CV mortality) and the Framingham function (any-CV-event). Results 1452 evaluable patients (863 men, 60.9%), aged 40.7±12.2 years and with a mean duration of illness of 15.5±10.8 years (mean±SD), were included. MS was present in 24.6% [23.6% (men), 27.2% (women); p =0.130]. Overall 10-year risks were 0.9±1.9 (SCORE) and 7.2±7.6 (Framingham). Coronary heart disease (CHD) 10-year risk was higher in MS patients: 6.6% vs 2.8% showed high/very-high CV mortality risk (SCORE≥3%), and 44.2% vs 12.9% high/very-high CV event risk (Framingham≥10%) (p <0.001). MS patients also had more psychopathology (PANSS) and greater severity (CGI). Conclusions MS is highly prevalent in antipsychotic-treated patients and is associated with increased cardiovascular risk and psychopathology.