Objective: Obesity is associated with both increased breast cancer risk and poorer prognosis after disease onset. Women who are obese continue to have higher levels of estrogen than women of normal weight even after treatment with hormone-suppressing drugs, raising the possibility that they might benefit from modification or changes to their treatment. The aim of this work was to study the effect of letrozole compared to tamoxifen on serum estradiol and, vitamine D and metabolic profile in Iraqi obese postmenopausal women with breast cancer. Methods:A hospital-based case-control study was carried out at Baquba teaching hospital, Diyala, Iraq. The analyzed variables were: age, lipid profile including total cholesterol; triglycerides, HDL-C, blood sugar, estradiol, and serum vit D. Descriptive statistics and testing of hypothesis were used for the analysis using mean±SD test P≤0.05. Results:Lipid profile, serum estradiol showed significant variability among the studied group in this study and serum vit D show significant differences between groups in postmenopausal obese with breast cancer taking tamoxifen. Conclusion:Treatment of obese women with breast cancer with tamoxifen or letrozole had neglected effects on metabolic parameters including lipid profile and blood sugar, both agents decrease serum estradiol level in treated patients, and most importantly, the significant positive effect of tamoxifen on serum vitamin D level compared to negative effect of aromatase inhibitor drug letrozole.