Abstract: Introduction: Despite the strong association between HLA-B51 and Behcet’s disease (BD), the clinical significance of this genetic marker has not been fully elucidated. The aim of this study was to find out the association of HLA-B51 with various manifestations of BD, and to compare it to those of HLA-B5. Patients & methods: All newly diagnosed BD patients in a 9-month period from April 2001 to January 2002 were studied. They were classified into two groups according to the presence or absence of HLA-B51. Different manifestations of the disease, including 100 clinical and paraclinical data were compared between the two groups by chi square test and Fisher exact test. A confidence interval at 95% (CI) was calculated for each item. The same comparison was made for the B5 positive and negative BD patients. Results: Of 201 new BD patients studied, 78 (39%, CI:6.7) were B51 positive. The childhood onset of the disease (before 16) was surprisingly lower in B51+ patients (9%6.4 vs. 25%7.7, p<0.003). There were no significant difference between the two groups for presenting signs, or any clinical or paraclinical manifestations. The same analysis was done for 4531 registered BD patients in our database. B5+ patients had a higher frequency of male patients (p<0.005), ocular (p<0.009), articular (p<0.007), G.I (p<0.02), CNS (p<0.008) manifestations, epididymitis (p<0.04), and positive Pathergy test (p<0.00006). Conclusion: In contrast to the effect of B5, the lack of association of B51 to the disease expression in new BD patients may be due to their low number and lower disease duration. The delaying effect of B51 on the disease onset has never been noticed previously.