ARTICLE ABSTRACTBackground: Metabolic syndrome and its component feature, central obesity, are associated with endometrial cancer risk. It remains unclear whether associations with the other metabolic factors that comprise metabolic syndrome are independent of the obesity–endometrial cancer association. Furthermore, the link with specific endometrial cancer subtypes remains ill-defined, despite evidence of etiologic heterogeneity among these tumors.Methods: In a case–control study within the SEER–Medicare linked database, we examined whether metabolic factors, individually or combined, were associated with endometrial cancer. Cases (n = 16,323) were women diagnosed with endometrial cancer from 1993 through 2007. Controls (n = 100,751) were a 5% sample of female Medicare enrollees residing in the same SEER registry area as cases. Metabolic syndrome was defined using ICD-9-CM codes from inpatient/outpatient diagnoses 1 to 3 years before case diagnosis and a comparable time period in controls. ORs and 95% confidence intervals (CI) were estimated using logistic regression.Results: Endometrial cancer risk was associated with metabolic syndrome [OR (95% CI): 1.39 (1.32–1.47)] and its component factors: overweight/obesity [1.95 (1.80–2.11)], impaired fasting glucose [1.36 (1.30–1.43)], high blood pressure [1.31 (1.25–1.36)], and high triglycerides [1.13 (1.08–1.18)]. After adjusting for overweight/obesity, the increased risks associated with the metabolic syndrome factors remained. Heterogeneity of associations by subtype were not identified (Pheterogeneity = 0.82).Conclusions: Among women age 65 and older in the United States, metabolic syndrome, and its component factors, increased endometrial cancer risk similarly across endometrial cancer subtypes.Impact: Strategies to reduce the prevalence of metabolic syndrome factors might have a favorable effect on endometrial cancer incidence. Cancer Epidemiol Biomarkers Prev; 24(1); 261–7. ©2015 AACR.