Purpose: To evaluate the potential of proton therapy in sparing cardiac/coronary structures when compared with 3-dimensional conformal radiation therapy (3DCRT), helical tomotherapy (HT), and intensity-modulated radiation therapy using volumetric modulated arc therapy (VMAT). Materials and Methods: Comparative treatment planning was performed using computed tomography scans of 10 patients with left-sided stage III breast cancer after mastectomy, targeting the chest wall, axilla levels I to III, and the supraclavicular and internal mammary nodes (IMN) to 50.4 Gy (radiobiologic equivalent [RBE]) in 28 fractions. Organs at risk were heart, lungs, contralateral breast, unspecified healthy tissues, and coronary arteries. Plans were also compared that included IMNs for protons, but not for photons. Results: Mean heart dose of 1.2 Gy (RBE) was lowest with protons when compared with 6.8, 10.2, and 8.2 Gy for 3DCRT, HT, and VMAT, respectively (P , .05). The mean left anterior descending artery (LAD) dose was 7.0 Gy (RBE) for protons and lowest compared with 20.9, 14.8, and 15.6 Gy, respectively (P , .05). Total lung V5 Gy (RBE) was significantly lower with protons at 19.5% compared with 31.5%, 45.3%, and 54.0%, respectively (P , .05). Mean contralateral breast dose of 0.6 Gy (RBE) for protons was similar to 0.5 Gy for 3DCRT (P value not specified) but was significantly lower than 5.1 and 3.8 Gy for HT and VMAT (P , .05). Proton plans with IMN inclusion compared favorably to 3DCRT, intensity-modulated radiation therapy, and HT without IMN inclusion, with mean heart and mean LAD artery doses of 1.2 and 7.0 Gy (RBE) for protons versus 4.0 and 12.8 Gy for 3DCRT, 6.6 and 17.2 Gy for VMAT, and 7.4 and 11.4 Gy HT (P , .05). Conclusions: Proton therapy provided maximum cardiac and coronary sparing, even when compared with photon plans not including IMNs, thus, allowing treatment of the IMNs without increased risks to heart and coronary arteries. Reduced dose to lungs, contralateral breast, and healthy tissues indicates a reduced risk for development of second malignancy.