Abstract Introduction Electron beam radiation is the modality most often used to deliver an operative bed boost to breast cancer patients after completing whole breast radiation. However, electrons can potentially provide inadequate coverage. The MammoSite breast brachytherapy applicator may provide dosimetric advantages in the delivery of an operative bed boost and its role in this setting is not yet defined. Materials and methods The study population consisted of 15 patients with early stage breast cancer treated with partial breast irradiation (PBI) using the MammoSite device. For each patient, a theoretical boost plan using electrons and a second theoretical boost plan using the MammoSite applicator were created. To assess the adequacy of each boost plan, the PTV V90, PTV V95, and PTV V100 were calculated. To assess dose to normal tissues, the ipsilateral breast V50, ipsilateral lung V30, and heart V20 were calculated. Results The mean PTV V100 for the MammoSite boost was 95.5%, compared to 77.4% for the electron boost ( p < 0.001). The mean PTV V95 was 97.8%, compared to 93.3% for the electron boost ( p = 0.02). The mean PTV V90, mean breast V50, mean lung V30, and mean heart V20 were not statistically different for MammoSite compared to electrons. Conclusions A tumor bed boost using the MammoSite breast brachytherapy applicator provides superior target coverage and delivers similar doses to the ipsilateral breast and lung compared to a boost delivered with electrons. More investigation into the role of balloon brachytherapy in the delivery of a breast boost is warranted.