Smoking is suspected of altering host immunity and may therefore hasten the development of metastases among cancer patients. The authors followed 946 patients with melanomas of the choroid and/or ciliary body who had been treated with proton beam irradiation and who had provided a smoking history during their evaluation before treatment. After a mean follow-up of 33 months, 98 patients were diagnosed with metastatic disease. Metastasis-free survival rates 3 years after irradiation were similar in association with never, past, and current cigarette smoking (86%, 89%, and 90%, respectively; P = 0.90). Rates also were similar with increasing pack-years of exposure and when the product smoked was cigarettes versus pipes or cigars only. Estimates for smoking effects were unchanged after adjusting for established prognostic factors for metastases. Results suggest that smoking does not alter the risk of metastases during the first few years after irradiation of choroidal melanomas.