Background: Whether subjects with metabolically healthy obesity (MHO) have an increased risk of cardiovascular disease (CVD) is controversial. Some of this discrepancy could be due to differences in the definition of MHO. Therefore, we investigated how the definition of MHO affected the risk of CVD. Methods: In the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort (total n = 2122, mean age 50 years), obese (n = 134), overweight (n = 845), and normal weight (n = 1143) individuals were subdivided according to the number of Metabolic Syndrome (MetS) risk factors (excluding waist circumference). During a median follow-up of 28.0 years, 877 individuals experienced a CVD event (defined as fatal or nonfatal myocardial infarction, stroke, or heart failure). Results: All obese groups, except that without any MetS risk factors (n = 3), showed an increased risk compared to the control group of normal weight without any MetS risk factors (n = 235), ranging from a hazard ratio (HR) of 3.0 (95% confidence interval [CI] 1.7-5.3, P = 0.0002) in those with one MetS risk factor to HR 5.5 (95% CI 3.0-9.8, P < 0.00001) in those with four MetS risk factors. The overweight group without any MetS risk factor (n = 74) showed a similar risk of incident CVD as the normal weight group, whereas all other overweight groups showed an increased risk with increasing number of MetS risk factors. Conclusions: The results suggest that the definition of MHO played a major role on the risk of CVD. No increased risk was seen in overweight/obese individuals with no MetS risk factor, but they were very rare.