Objectives To define the natural history of patients with isolated metabolic syndrome (MS). Patients and Methods Metabolic syndrome is associated with increased risk of cardiovascular mortality. Patients with isolated MS are a subset of patients with MS who do not meet the diagnostic criteria of hypertension (HTN) and diabetes mellitus (DM). Data were collected prospectively on a population-based random sample of 1042 Olmsted County, Minnesota, residents aged 45 years or older who underwent clinical evaluation, medical record abstraction, and echocardiography (visit 1: January 1,1997, to December 31, 2000). The cohort was subdivided into healthy controls, those with isolated MS, and those with MS with HTN and/or DM groups. After 4 years, patients returned for visit 2 (September 1, 2001, to December 30, 2004). After visit 2, we have a median of 8.3 years of follow-up. Results There was a higher incidence of HTN, DM, and obesity in the isolated MS group at visit 2 (P<.001) than in healthy controls. Patients with isolated MS did not have significantly higher rates of cardiovascular mortality (hazard ratio [HR], 0.85; 95% CI, 0.23-3.13; P=.80) or development of heart failure (HR, 1.29; 95% CI, 0.58-2.73; P=.53) compared with healthy controls over 8 years of follow-up after visit 2. However, patients with MS with HTN and/or DM had higher rates of cardiovascular mortality (HR, 2.40; 95% CI, 1.00-5.83; P=.02) and heart failure (HR, 2.24; 95% CI, 1.16-4.32; P=.02) compared with healthy controls over 8 years of follow-up after visit 2. Conclusion Isolated MS was associated with increased risk for the development of HTN, DM, and obesity, but not increased mortality or heart failure over an 8-year period compared with healthy controls. Future studies should determine whether aggressive management of risk factors in isolated MS will prevent progression to MS.