Abstract: Introduction: Iran is among the countries with high prevalence of Behcet's Disease (BD). The epidemiological survey on different aspects of the disease has been continuously carrying out since 1975 in our center. The aim of this study was to find if the characteristics of the disease are changing through the time. Patients & Methods: In a cohort of 4130 patients with BD, registered at our BD unit during the past 25 years, two groups were selected according to the time of their first visit. 1- Patients seen between 1975 to March 1991 (old group). 2- Patients seen between March 1993 to December 1999 (recent group). We introduced a time lag of 2 years between the two groups and omitted the patients seen during that time to intensify a possible difference. Different manifestations of the disease, including 100 clinical and paraclinical parameters, were compared by the chi square test. Results: There were 1777 patients in the old group. They were compared with 1655 patients in the recent group. There was no difference in the male to female ratio and the age of onset between the 2 groups. The mean disease duration (42+4.4 vs. 1.2+1.4, p<0.000001) and the mean follow up time (10.3+7.4 vs. 7.5+5.8, p<0.000001) were higher in the old group. As the first manifestation, oral aphthosis was seen less in the old group, while uveitis and joint manifestations were more common; both statistically significant (p<0.000001). The old group was associated with a lower frequency of mucous lesions (p<0.00004), notably oral aphthosis (p=0.000006); while the following lesions were seen with higher frequency: ocular, skin lesions especially pseudofolliculitis, vascular, joint, GI involvements (all with p<0.000001), neurologic (p<0.008), pulmonary (p<0.03), and cardiac involvement (p<0.002). Laboratory findings showed higher frequency of positive pathergy test (p<0.03), urinary abnormalities (p<0.009), and false positive VDRL (p=0.000005) in the old group. The other clinical and paraclinical data showed no significant difference between the two groups. Conclusion: Patients diagnosed in Iran as BD, in recent years, had milder forms of the disease. This may have 3 explanations: 1- the clinical pattern of BD is slowly changing. 2- Mild cases are diagnosed more frequently as physicians in Iran become more familiar with the disease. 3- the percentage of organ involvement increases with the disease duration.