ObjectiveThis study was conducted to compare the relative, clinical intraocular dose distribution for palladium-103 (103Pd) versus iodine-125 (125I) ophthalmic plaque radiation therapy.MethodsPreoperative comparative radiation dosimetry was performed to evaluate 319 consecutive uveal melanomas treated between 2006 and 2012.ResultsThere were 68 (21.3 %) anterior (iris and/or ciliary body) and 251 (78.7 %) choroidal melanomas examined in this study. According to AJCC staging, 7th edition, 146 (45.8 %) were T1, 126 (39.5 %) T2, 40 (12.5 %) T3, and 7 (2.2 %) T4. All were prescribed an equivalent tumor-apex dose. When compared to 125I, 103Pd was associated with a mean 41.9 % lower radiation dose to the opposite eye wall (p < 0.001), 12.7 % to the lens center (p < 0.001), 7.5 % to the optic disc (p = 0.008), and a 3.8 % decrease to the fovea (p = 0.034). However, subgroup analysis of smaller (T1-staged) tumors showed greater dose reductions to normal ocular structures compared to larger (T4-staged) tumors. Tumor and therefore plaque location also affected intraocular dose distribution. For example, palladium-103-related dose reductions to the fovea, optic nerve, and opposite eye wall were significantly greater for iris and ciliary body tumors compared to posterior choroidal melanomas (p < 0.001). After comparative dosimetry, 98.7 % (n = 315/319) were treated with 103Pd.ConclusionPreoperative comparative radiation dosimetry was performed for a large cohort of patients with uveal melanoma. It influenced radionuclide selection, offered an opportunity for radiation sparing of critical vision-related intraocular structures, and typically increased radiation within the tumors.