Introduction: Describe and evaluate characteristics of ocular tumor lysis syndrome (OTLS) in eyes with uveal melanoma. Methods: Retrospective chart review of all patients with OTLS at the University of Colorado from 2009-2021. Data collected included patient demographics, tumor characteristics, radiation dosimetry, gene expression profiling, OTLS characteristics, management, outcomes. Results: Seven eyes of seven patients with uveal melanoma treated with I-125 brachytherapy developed OTLS. Average age was 59 years (range 32-83). Mean apical height was 8.6mm (range 6-11); mean diameter was 12.7mm (range 8.5-15.3). All tumors were treated with plaques ≥16mm in diameter. On presentation, 5/7 tumors had subretinal fluid, and 6/7 had collar-button configuration. OTLS presented as extensive pigment dispersion in the vitreous in all eyes, subretinal pigment and/or retinal detachment in 4/7 eyes, vitreous hemorrhage in 2/7 eyes, anterior chamber pigment in 3/7 eyes. Four tumors were GEP class 1, two were class 2, one was unclassified. Biopsy route was trans-scleral in 4/7 eyes and trans-vitreal in 3/7 eyes. OTLS occurred 2-4 weeks after an intraocular procedure in 5/7 eyes. All underwent pars plana vitrectomy. Cytology of the vitreous, obtained in five cases, showed pigment laden macrophages and hemorrhage, but only 1/5 eyes had viable malignant cells. Four eyes were stable at last follow-up, two were enucleated, one was no-light-perception from pigmentary glaucoma. Poor vision (<20/200) occurred in 6/7 cases. Three patients died from metastasis (tumors were GEP class 2, GEP class without subclassification, and no GEP classification performed). Conclusions: OTLS is a rare but devastating complication of uveal melanoma. Common characteristics included large plaque diameter, presence of subretinal fluid, and collar-button shape. The extensively dispersed pigment is typically not malignant. Though poor vision is common, enucleation may be avoided in most eyes through vitreoretinal surgical repair.