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Vitreous seeds are the most challenging aspect in the management of retinoblastoma. We report the outcomes of treatment with proton beam radiation therapy (PBRT) for retinoblastoma with vitreous seeds in naive or previously treated eyes. In this retrospective case series, we analyzed data of 4 retinoblastoma patients with vitreous seeds who received PBRT at the Proton Therapy Center, National Cancer Center in Korea between June 2007 and August 2017. All 4 eyes treated by PBRT were classified as group D according to the International Classification of Retinoblastoma (ICRB) criteria, and the vitreous seeds, as class 3 (clouds). The tumor and vitreous seeds regressed in 2 eyes, and globe salvage was achieved in these 2 eyes (50%). The post-PBRT ophthalmologic follow-up time of these 2 preserved eyes was 12 and 50 months, respectively. Visual acuity measurements of the successfully treated patients were 20/40 and 20/600. No radiation-associated malignancies were noted. In conclusion, PBRT successfully treated vitreous seeds classified as clouds in half of the cases, and successfully treated patients who retained useful vision. Therefore, PBRT might be a viable treatment option for vitreous seeds in patients with retinoblastoma.