This study aimed to evaluate the effects of multi-leaf collimator angle change on the dosimetric parameters of the medial, central, and lateral tumor bed boost in hypofractionated left whole-breast irradiation with dynamic multi-leaf collimator technology. Sixty patients with early breast cancer following conservative surgery who underwent hypofractionated radiotherapy with tumor bed boost were enrolled from The First People’s Hospital of Zunyi between January 2018 and January 2023. All patients were classified into three groups according to the location of the tumor bed: medial, central, and lateral. The differences in target volume and cardiopulmonary dosimetric parameters between the plan of multi-leaf collimator angle change (labeled as Plan-A) and the original plan of 0° multi-leaf collimator angle (labeled as Plan-O) were compared in each group. The results did not show any significant differences in the coverage of the target prescription, conformability index, and homogeneity index between Plan-A and Plan-O of the three groups. In the medial group, the left lung V₅, V₁₀, and D_mean; heart V₈ and D_mean; and left anterior descending artery (LAD) D_max and D_mean of Plan-A were significantly lower than those of Plan-O (p<0.05). Meanwhile, in the central and lateral groups, only the LAD D_max and D_mean of Plan-A decreased significantly in the lateral group, and no differences were observed in other cardiopulmonary parameters compared to those in Plan-O (p<0.05). In conclusion, the change in collimator angle did not have a significant effect on the target dosimetric parameters of hypofractionated radiotherapy with tumor bed boost for the left breast. On the contrary, it could significantly reduce the cardiopulmonary dose in the medial group compared to the original radiotherapy plan. Given this information, it is recommended to change the multi-leaf collimator angle for the radiotherapy plan of the medial tumor bed group in left whole-breast hypofractionated radiotherapy.