The authors evaluated a series of 145 consecutive patients with metastases from uveal melanoma, after proton beam irradiation, to assess the effect of early diagnosis and treatment for metastases on survival. Metastases were diagnosed between 7 weeks and 8.3 years (median, 2.4 years) after proton beam irradiation. Most patients (n = 94) were symptomatic before diagnosis; the remainder were first detected during screening examination. Liver involvement was documented in nearly all patients (n = 136). The majority of patients had died from metastases by the close of the study (n = 137). Significantly longer survival occurred among patients diagnosed during screening examination (P = 0.004) and among young patients (P = 0.03). The majority of patients received some form of treatment for metastases (69%). Median survival was 2.0 months for patients receiving no treatment compared with 5.2 months for those receiving treatment for metastases (P = .0001). However, the overall 1-year survival rate was poor (13%). Prophylactic adjuvant therapy could be explored as a means to increase disease-free survival in patients with uveal melanoma.