Abstract Obesity and obesity-related metabolic disorders, such as diabetes and chronic inflammation, have been positively associated both with postmenopausal breast cancer and with resting energy expenditure (REE). However, there is limited epidemiologic evidence on the associations between REE and risk of postmenopausal breast cancer. We used multivariable Cox proportional hazards models to examine the association between predicted REE (calculated using the Ikeda, Livingston, and Mifflin equations) and risk of postmenopausal breast cancer overall and by subtypes, and by level of body fat) among 137,283 postmenopausal women in the Women's Health Initiative (WHI). All predicted REEs were positively associated with risk of invasive breast cancer [HRq5 vs. q1 = 1.69; 95% confidence interval (CI), 1.57–1.81; HR = 1.69; 95% CI, 1.57–1.82; and HR = 1.68; 95% CI, 1.56–1.80 for Ikeda, Livingston, and Mifflin, respectively]. These positive associations were observed irrespective of the hormone receptor subtype, grade, and stage of the tumors, but were most pronounced for estrogen receptor–positive/progesterone receptor–positive tumors. After additional adjustment for body mass index (BMI), the associations were mostly attenuated and remained statistically significant for most of the outcomes. We also observed an interaction between the predicted REEs and BMI, with the associations being somewhat stronger among normal weight and overweight women than among obese women (Pinteractions < 0.05). Our findings indicate that relatively high REE is associated with increased risk of invasive breast cancer among postmenopausal women (particularly for the obesity-related tumor subtypes), irrespective of the equation used. Further studies using more objective measures of REE are, however, needed to confirm our findings. Prevention Relevance: This study showed that higher resting energy expenditure (REE) was associated with higher postmenopausal breast cancer risk. REE provides energy to support cancer-associated disorders such as obesity and inflammation. Thus, studies on its association with breast cancer can help to improve our understanding of the pathophysiology of breast cancer.