Introduction: Vision loss is common in patients treated with radiotherapy for uveal melanoma. With proton beam irradiation (PBI), the prescribed dose is delivered to the tumor with a sharp dose reduction outside the target volume. However, radiation complications are likely to develop when tumors are located near the optic nerve or fovea. Treatment with light-activated AU-011 (belzupacap sarotalocan), an investigational drug which specifically targets tumor cells, may avoid these complications. We evaluated outcomes in a historical group of patients who fit eligibility criteria for AU-011 therapy and were treated with PBI. Methods: A consecutive series of patients who received PBI for small choroidal melanoma at a single center between 1986 and 2016 were identified. Consistent with eligibility criteria in clinical trials of AU-011, patients were included when tumor dimensions did not exceed 2.5 mm in maximum thickness and 10.0 mm in largest basal diameter (LBD). Snellen visual acuities were converted to logMAR for analysis. Visual acuity outcomes were analyzed in patients with an initial acuity of logMAR 0.7 or better (equivalent to Snellen 20/100). Rates of visual acuity loss and mortality were calculated using the Kaplan-Meier method. Acuity loss by tumor location was compared using log-rank testing. Rates of tumor recurrence, neovascular glaucoma (NVG), and eye loss were also described. Results: Two hundred and 22 patients were included in the study. The median age was 60.7 years (range 21.3–94.8 years). Median tumor thickness was 2.0 mm (range 1.2–2.5 mm), and median LBD was 8.0 mm (range 4.0–10.0 mm). Median follow-up was 6.9 years (range 1.0–30.2 years). In 204 patients with a baseline logMAR visual acuity of 0.7 or better, the mean baseline acuity was 0.15 (equivalent to Snellen 20/25), which decreased to 0.52 (approximately Snellen 20/70) by 5 years after PBI. Visual outcomes were significantly worse for patients with tumors located within 3 mm of the optic disc and/or fovea. Tumor recurrence (1.4%), NVG (4.5%), and eye loss (2.7%) were uncommon. Discussion: Despite the advantageous dose distribution of protons, over half of patients with small choroidal melanomas located near the optic disc or fovea had a visual acuity equivalent to 20/80 or worse at 5 years after PBI. Treatment with AU-011 may allow better vision preservation in small tumors that carry a high risk of vision loss with radiotherapy.