Objective: To investigate the safety and efficacy of external scleral plaque radiotherapy (PRT) in the treatment of uveal melanoma (UM). Methods: This was a retrospective case series study. The data of 819 patients who underwent ophthalmic PRT from July 2007 to November 2017 at Tongren Hospital Affiliated to Beijing Capital Medical University was collected, including preoperative visual acuity, intraocular pressure and slit lamp microscope, color fundus photography, indirect ophthalmoscopy, color Doppler ultrasound, fundus fluorescein angiography, indocyanine green angiography, orbital nuclear magnetic resonance imaging, PRT times and time, complications, follow-up time, the maximum basal diameter and height of the tumor UM half a year after the applicator was removed, tumor metastasis rate, mortality and visual acuity observed at the last follow-up. The tumor growth was considered when the tumor height increased by 2.0 mm or the extension of any boundary of the tumor was 2.5 mm; otherwise, the treatment was defined as effective. The paired t test and Kaplan-Meier survival curve were used for statistical analysis. Results: There were 408 males and 411 females. The age ranged from 13 to 85 years (mean, 47 years). Nine patients had ciliary body melanoma, 43 patients had choroidal melanoma involving the ciliary body, and 767 patients had choroidal melanoma. In all 819 eyes, the tumor was medium-sized in 697 eyes and large in 110 eyes. All patients were treated with PRT only one time. The average radiotherapy time was 15 days (range, 6 to 50 d). All operations were successfully completed, with no active bleeding, infection, adjacent tissue injury and other related complications. At 6 months after the treatment, the maximum basal diameter of the tumor was (12.41±3.20) mm, which was significantly different from that before treatment (12.82±3.21) mm (t=2.40, P<0.01); the tumor height was (6.18±2.55) mm, which was significantly different from that before treatment (7.21±2.57) mm (t=4.05, P<0.01). The average follow-up time was (34±24) months (range, 1 to 125 months). Twenty-five patients lost follow-up at 2 years after the PRT, and 71 patients underwent enucleation. The effective rate of the PRT treatment was 88.3% (723/819), and the eyeball retention rate was 91.1% (723/794). The visual acuity remained stable in 393 eyes, decreased in 344 eyes, and improved in 82 eyes. Sixty patients had systemic metastasis (liver, bone or breast metastasis). Twenty-two patients died of tumor metastasis. The 5-year metastasis rate was 12.8%; the 5-year mortality rate was 5.8%; the 10-year metastasis rate was 20.6%; the 10-year mortality rate was 5.8%. Conclusions: PRT is safe and effective in the treatment for UM and can preserve some useful visual acuity. PRT can be used as the main treatment for medium-sized UM.(Chin J Ophthalmol, 2020, 56: 670-675).