Background: This study aims to evaluate the risk of hypothyroidism (HT) after radiotherapy (RT) of breast and supraclavicular in patients with breast cancer (BC). Materials and Methods: In a historical cohort study, the records of all patients with BC who had been referred to the Mahdieh radiotherapy Center of Hamadan from 2017 to 2019 were reviewed. Demographic characteristics, clinical information, previous and current used treatment methods (surgery, radiotherapy, chemotherapy), number of RT sessions and doses, and HT (TSH >5 mIU/L) were extracted from the patient's documents. Data were analyzed using SPSS software version 16. Results: Out of 304 patients referred to the Center, 266 patients were investigated. The mean TSH was 6.3 ± 7.9 ml/L (1.5 to 65.4). Approximately half of the patients were in Stage 2 of the disease. 37 (16.4%) patients were diagnosed with HT, of which 8.8% were clinical, and 7.5% were subclinical. The mean total dose of HT patients (5621.62 ± 491.67) was significantly higher than other patients (5304.76 ± 937.98). 21 patients (56.8%) in Stage 3 and 4 and 16 (43.2%) patients in Stages 1 and 2 had HT (P = 0.006). Spearman correlation coefficient showed that there was a significant relationship between total dose and TSH hormone (r = 0.624), the number of RT sessions with TSH hormone (r = 0.237), and total dose with T4 hormone (r = -0.232). Conclusion: The findings of this study showed that the risk of HT increases significantly in patients with BC who undergo RT of breast and supraclavicular. Patients with higher stage, more radiation, and more RT sessions are at higher risk of HT.