The metabolic syndrome has been criticized for being "polluted with the inclusion of frank "diseases" with "pre-diseases". We assessed the effect of a single and a combination of "pre-disease" risk factors of metabolic syndrome on the overall and cardiovascular disease (CVD) mortality. These pre-disease risk factors included pre-diabetes, pre-hypertension, overweight and borderline hypertriglycerdemia and were defined as: fasting glucose at 110-125 mg/dL, systolic blood pressure at 120-139 mmHg, body mass index at 25-29.9 kg/m(2) and serum triglyceride at 150-199 mg/dL, respectively. The metabolic syndrome in this paper was based on the version defined by the ATP III. The cohort consisted of 35,259 adults (>==40 years) with a medium follow-up of 15 years. Relative risks (RRs) for all-causes, CVD and "CVD plus diabetes" mortality were calculated with the Cox proportional hazards model. Prevalence of the pre-disease risk factors (40.2%) was nearly four times larger than the metabolic syndrome (10.6%). Individual pre-disease risk factor was associated with significant increases of 13% and 67% (pre-diabetes), 22% and 62% (pre-hypertension), 23% and 32% (overweight) and 17% and 46% (borderline hypertriglyceridemia) on all-cause and "CVD plus diabetes" mortality, respectively. Smoking had comparable risks as "pre-diseases", and, as such, should also be considered as the fifth "pre-disease". Like metabolic syndrome, each "Pre-disease" is a major and significant risk factor for all cause and cardiovascular mortality, but unlike metabolic syndrome, the definition or clinical follow up of "Pre-disease" is simple and straightforward. Recognizing each of the four "pre-disease" as a clinical entity, a hitherto sub-clinical status but involving significantly increased mortality, can alert and justify early intervention through changing lifestyle and modifying biologic risk factors.