Abstract: Cytotoxic drugs are the gold standard and the first line treatment for ophthalmological manifestations of Behçet’s Disease (BD). The purpose of this study was to evaluate eyes with chlorambucil on long-term follow-up, in a longitudinal study on 15 years. Methods: Chlorambucil was given as 0.2 to 0.3 mg per kilogram of body weight and per day. Prednisolone was concomitantly given as 0.5 mg per kilogram of body weight. Prednisolone was tapered later according to the improvement of inflammation. In refractory cases, the patient was switched to another cytotoxic drug. Visual acuity (VA) was calculated on a Snellen chart (on a scale of 10). A Disease Activity Index (DAI) was calculated for anterior uveitis (AU), posterior uveitis (PU), and retinal vasculitis (RV) according to Ben Ezra. The Total Inflammatory Activity Index (TIAI) and the Total Adjusted Disease Activity Index (TADAI) were also calculated. Results, before the treatment and after different intervals (from 3 months to 15 years), were compared together by t percentages. Results: Eighty nine patients received chlorambucil. The mean duration of treatment was 26.2 months ±2.6. Good results (stabilized or improved eyes from the baseline to last evaluation) were: VA 68.4%, PU 87.6%, RV 75.8%, TIAI 85.4%, TADAI 76.4%. The mean VA improved from 2.6 to 3.3, mean PU improved from 1.8 to 0.7, mean RV improved from 2.1 to 1.5, mean TIAI improved from 13.9 to 7.6, and mean TADAI improved from 21.5 to 16.2. The difference was statistically significant fo study time. Conclusion: Chlorambucil with prednisolo