Background. While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause specific cardiovascular outcomes with regard to low fasting glucose in the general population. Objective. We hypothesized that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women. Methods. To test our hypothesis, we used both continuous incidence rates and Cox proportional hazards models in 17,287 participants from the Women's Health Initiative with fasting glucose measured at baseline. Participants were separated into groups based on fasting glucose level: low (= 126 mg/dL). Results. Participants were free of cardiovascular disease at enrollment, had mean age of 62 years, and were 52% Caucasian, 24% African American, 8% Asian, and 12% Hispanic. Median follow-up was 15 years. Graphs of continuous incidence rates compared to fasting glucose distribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fasting glucose were positively associated with all outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR = 0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant. Conclusions. Fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality. (C) 2017 Elsevier Inc. All rights reserved.