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To compare the effects of a caloric restriction (CR) on body composition, lipid profile, and glucose homeostasis in obese postmenopausal women with and without metabolic syndrome (MetS).Secondary analyses were performed on 73 inactive obese postmenopausal women (age 57.7 ± 4.8 years; body mass index 32.4 ± 4.6 kg/m2) who participated in the 6-month CR arm of a study of the Montreal-Ottawa New Emerging Team. The harmonized MetS definition was used to categorize participants with MetS (n = 20, 27.39%) and without MetS (n = 53, 72.61%). Variables of interest were: body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), glucose homeostasis at fasting state and during a euglycemic/hyperinsulinemic clamp, fasting lipids, and resting blood pressure.By design, the MetS group had a worse cardiometabolic profile, whereas both groups were comparable for age. Fifty-five participants out of 73 displayed no change in MetS status after the intervention. Twelve participants out of 20 (or 60.0%) in the MetS group had no more MetS after weight loss (P = NS), whereas 6 participants out of 53 (or 11.3%) in the other group developed the MetS after the intervention (P = NS). Overall, indices of body composition and body fat distribution improved significantly and similarly in both groups (P between 0.03 and 0.0001). Furthermore, with the exception of triglyceride levels and triglycerides/high-density lipoprotein cholesterol ratio, which decrease significantly more in the MetS group (P ≤ 0.05), no difference was observed between groups for the other variables of the cardiometabolic profile.Despite no overall significant effects on MetS, heteregeneous results were obtained in response to weight loss in the present study, with some improving the MetS, whereas other displaying deteriorations. Further studies are needed to identify factors and phenotypes associated with positive and negative cardiometabolic responses to CR intervention.