Obesity is a major risk factor for several metabolic diseases, frequently clustering to form the metabolic syndrome, carrying a high risk of cardiovascular mortality. We aimed to assess the prevalence of the metabolic syndrome in treatment-seeking obese subjects and the potential protective effect of physical activity. A cross-sectional analysis of data from a large Italian database of treatment-seeking obese subjects was performed. The metabolic syndrome was defined according to the criteria provisionally set by the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, based on waist circumference, fasting glucose, triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) levels, and arterial pressure. Data were available in 1,889 Caucasian subjects, 78% females, from 25 obesity centers. Minimum criteria for the metabolic syndrome were fulfilled in 53% of cases. The prevalence increased with age and obesity class and was negatively associated with participation in a structured program of physical activity (odds ratio, 0.76; 0.58 to 0.99; P =.041), after correction for age, sex, and body mass. The prevalence of cardiovascular disease was higher in subjects with the metabolic syndrome. A subset of 12.8% of cases had no metabolic abnormalities. They had a lower prevalence of abdominal obesity and cardiovascular disease. Isolated obesity was significantly associated with physical activity (odds ratio, 1.86; 1.33 to 2.60; P =.0003). Multiple metabolic disorders are present in most obese patients, and their prevalence is lower in physically active subjects. It is time to move towards a more integrated approach and to reconsider resource allocation to improve lifestyle changes for large-scale control of obesity.