Abstract Introduction Hyperinsulinemia and insulin resistance are known to be associated with increased cardiovascular morbidity and mortality. A metabolically unhealthy phenotype is frequently used as a surrogate marker for insulin resistance. The aims of the current study were to compare the prevalence of the body size phenotypes using different definitions of metabolic health and to investigate which one of them is most strongly associated with insulin resistance in men and women. Methods We conducted a cross-sectional study in a middle-aged cohort of Maltese Caucasian non-institutionalized population. Metabolic health was defined using the various currently used definitions. Results There were significant differences in the prevalence of body size phenotypes according to the different definitions. We also found significant sex differences in the predictive value of the various definitions of the metabolically unhealthy phenotype to predict insulin resistance. The strongest association was for the definition of having >2 NCEP-ATPIII criteria to characterize the metabolic unhealthy phenotype in women (odds ratio of 19.7). On the other hand, the Aguilar-Salinas et al. definition had the strongest association in men (odds ratio of 18.7). Conclusions We found large differences in the prevalence of the various body size phenotypes when using different definitions, highlighting the need for having standard criteria. Our data also suggest the need for sex-specific definitions of metabolic health.