PURPOSE To compare the efficacy of iodine-125 (125I) and ruthenium-106 (106Ru) episcleral plaque radiation therapy and proton beam radiation therapy (PBRT) in the treatment of choroidal melanoma. DESIGN A retrospective, nonrandomized comparative study. METHODS Charts of patients treated with 125I, 106Ru, and PBRT for choroidal melanoma between January 1988 and June 1996 at St. Bartholomew's Hospital and Moorfields Eye Hospitals were reviewed. MAIN OUTCOME MEASURE Local control of choroidal melanomas after 125I, 106Ru, or PBRT. RESULTS A total of 597 patients were identified (125I = 190, 106Ru = 140, PBRT = 267). Patients treated with 106Ru had a significantly greater risk of local tumor recurrence than did patients treated with either 125I (P = 0.0133; confidence interval [CI], 1.26-7.02; risk ratio, 2.97) or PBRT (P = 0.0097; CI, 1.30-6.66; risk ratio, 2.94). A stepwise Cox proportional hazard model found maximal basal diameter to be a significant covariate (P = 0.0033). CONCLUSION Patients treated with 106Ru had a significantly greater risk of local tumor recurrence than did those patients treated with either 125I or PBRT.