We evaluated response, progression-free survival (PFS), overall survival (OS), relapse patterns and long-term toxicity of intraocular lymphoma (IOL) patients treated with ifosfamide (IFO) or trofosfamide (TRO). In a prospective single center study, IFO or TRO were given to 10 patients with IOL. The median patient age was 73 (range 46–83) years. Six patients were pretreated with up to four treatment regimens for ocular or cerebral lymphoma, and four were therapy-naive. All patients responded, including nine complete remissions and one partial remission, with a median PFS of 18 (7–36) months. Seven patients relapsed: five in the eye and two in the brain. Median OS was 32 (7–37+) months. No long-term toxicity was observed in patients treated with IFO or TRO alone. IFO or TRO were active and well tolerated in this study. Thus, they may represent suitable combination partners for other cytostatics used for PCNSL and IOL treatment.