Purpose: To report the quality of life and visual functioning in uveal melanoma patients treated with enucleation or fractionated stereotactic radiation therapy (fSRT).Methods: Uveal melanoma (UM) patients treated with fSRT (n = 65) or enucleation (n = 48) participated in this prospective study. Questionnaires to measure anxiety (State-Trait Anxiety Inventory), subjective distress (Impact of Event Scale) and quality of life (EORTC-QLQ-C30 and National Eye Institute Visual Function Questionnaire (VFQ-25)) were obtained before treatment and 2, 6, 12, 24, 36 and 48 months after treatment.Results: Less peripheral vision was observed until 3 years (p = 0.026) posttreatment in enucleated patients compared to irradiated patients. From 2 months until 3 years posttreatment irradiated patients increase in role functioning-score (p = 0.005), while enucleated patients decrease in score (p = 0.012). Regardless of their treatment, for all patients we measured a reduction in physical functioning (p = 0.035), insomnia (p < 0.001) and in state anxiety from pretreatment until 2 years posttreatment (p < 0.001). An increase in pain overall (p = 0.023) and in emotional functioning is observed 1 year posttreatment (p < 0.001). At baseline, patients with metastases (independent of their treatment) have more subjective distress (p = 0.037) than patients without metastases. The mean 'global health score' overall, without effect of time, was 76.4 (SD: 13.6).Conclusion: Enucleated patients had more difficulty working or performing household tasks 2 months posttreatment compared to irradiated patients. Enucleated patients had diminished peripheral vision until 3 years compared to irradiated patients. Overall quality of life is not significantly different between both treatment groups.