Abstract: Introduction: Ocular lesions are the major cause of morbidity in Behcet’s Disease. If not treated they usually progress toward severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic arsenal used for this condition. Materials & Methods: In an open, non randomized control study, pulse Cyclophosphamide (PCP), low dose pulse cyclophosphamide (LDP), oral cyclophosphamide (OCP), weakly methotrexate (MTX), chlorambucil (CHL), and cyclosporine A (CYA) were used in a standard protocol for 856 patients. Inclusion Criteria were: 1- fulfilling the Iran criteria. 2- Having posterior uveitis (PU) and/or retinal vasculitis (RV). 3- Having an active inflammatory lesion of the eye. Total Inflammatory Activity Index (TIAI) was calculated for each patient on the inflammatory state of the anterior chamber, the uvea, and the retina. The threshold level for improvement of aggravation was set to 20% change of the entry data. PCP group: Patients: 328, mean follow-up (MFU): 20.4 months, TIAI 16.8 LDP group: Patients: 147, MFU: 14.3, TIAI: 21.2 OCP group: Patients: 41, MFU: 15.8, TIAI: 9.4 MTX group: Patients: 244 MFU: 18.7, TIAI: 12.7 CHL group: Patients: 76, MFU: 21.3, TIAI: 10.6 CYA group: Patients: 20, MFU: 23.9, TIAI: 17.2. Results: The percentage of cured or improved eyes, and the confidence interval calculated at 95%, for the VA was: PCP: 37+4.4, CHL: 37+7.8, CYA: 50+16. The percentage of patients in whom the TIAI improved was: PCP: 72.4+10.3, CYA: 85+16.7. Side Effects; PCP: 19%, LDP: 27%, CHL: 30%, CYA: 90%, OCP: 22%, MTX: 9%. Statistically there was no significant difference between results, except for side effects. Conclusion: MTX showed the lowest side effects, therefore we propose MTX as a first choice, especially in patients without RV. In RV, cyclophosphamide should be the first choice, Cyclosporine A must be left as a last resort, due to its high costs and side effects.