The aim of the study was to analyze the local efficacy and eye retention rate after frameless, image-guided robotic radiosurgery against uveal melanoma. A total of 217 patients, mostly with medium and large unilateral uveal melanomas (3% small, 62% medium, and 35% large) were treated. The median age was 64 years (range 21–95 years). All patients underwent a single-session procedure beginning with retrobulbar anesthesia, followed by MRI and computerized tomography scanning to generate the treatment plan. The tumor dose was 18–22 Gy (mean, 20.3 Gy) prescribed to the 70% isodose line. Follow-up occurred at 3, 6, 12, and 18 months and yearly thereafter with clinical, ultrasound, and MRI studies. The median follow-up time was 26.4 months. All patients were treated in the frameless setup within 3 h. The actuarial 3- and 5-year eye retention rates were 86.7 and 73%, respectively. Local control at 3 and 5 years was 87.4 and 70.8%, respectively. Serviceable vision was maintained in 30.9% of patients at last follow-up. Treatment-induced glaucoma developed in 33 patients at a median 20.8 months (range, 5.8–54.0 months). Other adverse effects were hemorrhage (26 patients) and macular edema (seven patients). Frameless, single-session, image-guided robotic radiosurgery is an effective and straightforward treatment option for patients with medium and large uveal melanoma that are otherwise difficult to treat.