Tamoxifen is an estrogen receptor modulator and has been shown to increase risk for microvascular flap complications. This study aimed to investigate the clinical and histopathological effects of tamoxifen use in venous microvascular anastomosis model in rats. The role of vitamin E combination therapy and discontinuing tamoxifen therapy preoperatively were also evaluated. Forty rats were equally divided into 4 groups as follows: group 1 was given saline by oral gavage, group 2 was given tamoxifen citrate, group 3 was given tamoxifen citrate and vitamin E, and in group 4, tamoxifen citrate was given everyday except between days 12 and 16. In each group, femoral veins were dissected in each side and end-to-end anastomosis was performed in one side. Clinical and histopathological evaluations were performed. The ratio of total endothelial area to total vein area in a cross-sectional view of the vein was evaluated and compared.