Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group (p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups (p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study.