Abstract Purpose The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). Methods Radiation oncologists from LAC were invited to contribute to this this study. A 38-question survey was used to evaluate their opinions. Results A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. For whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules. Conclusion Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.