Background: Radiotherapy of an eye before enucleation, so called preenucleation radiotherapy (PER), of patientswith uveal melanomawas initiated to reduce enucleation-induced systemic metastasis. Earlier studies with a short follow-up period have not demonstrated a significant effect on survival. Objective: To study the effect of PER on melanoma-related mortality after more than 9 years of follow-up. Design: In a prospective study, 167 patients with uveal melanoma were treated between 1978 and 1992 by irradiation with 800 rad (8 Gy) given in 2 fractions 2 days before enucleation. A group of 108 patients with uveal melanoma treated between 1971 and 1992 by enucleation only in the same hospital served as a historical control group. Patients were followed up until December 2002 or death. Results: Melanoma-related death occurred in 32.3% of the PER-treated group and in 40.7% of the enucleation only group. Mean follow-up was 9.25 years. After 48 months of follow up, a significant difference in survival became evident in favor of the PER group. The estimated 15- year survival rates for patients with melanoma in the PER group and enucleation only group were 63.7% and 51.0% , respectively. For patients dying of all causes, these percentages were 47.5% and 25.2% , respectively. In both groups, women had a better prognostic outcome than men. Conclusion: This study suggests that PER improves long-term survival in patients with uveal melanoma. Background: Radiotherapy of an eye before enucleation, so called preenucleation radiotherapy (PER), of patients with uveal melanomawas initiated to reduce enucleation-induced systemic metastasis. Earlier studies with a short follow-up period have not demonstrated a significant effect on survival. Objective: To study the effect of PER on melanoma-related mortality after more than 9 years of follow-up. Design: In a prospective study, 167 patients with uveal melanoma were treated between 1978 and 1992 by irradiation with 800 rad (8 Gy) given in 2 fractions 2 days before enucleation. A group of 108 patients with uveal melanoma treated between 1971 and 1992 by enucleation only in the same hospital served as a historical control group. Patients were followed up until December 2002 or death. Results: Melanoma-related death occurred in 32.3% of the PER-treated group and in 40.7% of the enucleation only group. Mean follow-up was 9.25 years. After 48 months of follow-up, a significant differen The estimated 15-year survival rates for patients with melanoma in the PER group and enucleation only group were 63.7% and 51.0%, respectively. For patients dying of all causes, these percentages were In both groups, women had a better prognostic outcome than men. Conclusion: This study suggests that PER improves long-term survival in patients with uveal melanoma.