Background: Uveal melanoma and its treatment can influence the physical and psychological well-being of patients in a way that differs from other cancers. Factors influencing quality of life (QOL) include visual impairment, changes in appearance, day-to-day functioning, ocular discomfort, and worry regarding disease recurrence. Objective: We aimed to study both general and disease-specific QOL in uveal melanoma patients in Ireland and compare QOL between a plaque radiotherapy group and an enucleation treatment group. This information was sought to enhance our understanding of QOL issues for uveal melanoma patients, in the context of improving care and providing appropriate psychosocial support. Method: The European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaires QLQ-C30 and QLQ-OPT30 were completed by patients with uveal melanoma treated by enucleation or brachytherapy. Results: 138 of 206 patients completed the questionnaires. There was no significant difference in QOL scores between treatment groups. Thirty-two percent of patients reported concerns about tumour recurrence elsewhere in the body. The brachytherapy group had a significantly higher “role functioning” score (p = 0.030). Enucleation patients were more likely to have problems with appearance (p < 0.0005). Younger patients (12–54 years of age) were more likely to report headaches (p < 0.0005) and problems with reading (p = 0.042), and they had a lower cognitive functioning score (p = 0.003) than those aged ≥55 years. Conclusions: There was no significant difference in reported QOL between treatment groups. Our data identified a number of vulnerable patient subgroups. By anticipating which patients are more likely to suffer in terms of certain aspects of their QOL, we are better able to provide appropriate and timely psychosocial support.