Abstract Background & Aim of the work: β-Thalassemia (βT) is highly prevalent in some countries like Egypt. Accurate data about actual disease prevalence and heavily prevalent geographic locations are essential to help in early detection and in setting up effective preventive programs. We aim for screening of βT carriers among Egyptian high school students in the Delta region. Subjects and methods: A cross-sectional multicenter study was carried on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for βT carrier status using high-performance liquid chromatography. Results: The total prevalence of βT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al-Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. Conclusions: Despite the premarital national screening program for βT in Egypt, the carrier rate is still high. More effort should be done for the proper implementation of national prevention programs. Keywords: Egypt; carrier; national prevention programs.; school children; screening; β-thalassemia.