OBJECTIVE To estimate the prevalence of sickle cell disorders and beta thalassemia, with their regional distribution, in the adult population screened as part of the Saudi Premarital Screening Program. METHODS A cross-sectional, population-based study was conducted as part of the National Premarital Screening Program. It covered all the individuals who applied for a marriage license during the years 1425 and 1426 Hijra (February 2004 to January 2005). A network of 123 reception centers in the Ministry of Health facilities and 70 laboratories all over Saudi Arabia was involved in data collection. RESULTS Of a total of 488,315 individuals screened, 4.20% had sickle cell trait, 0.26% had sickle cell disease, 3.22% had thalassemia trait, and 0.07% had thalassemia disease. Both the diseases were focused mainly in the eastern, western, and southwestern parts of the country. Among the 207,333 couples who were issued certificates for matching, 2.14% were declared high risk. Among the 2,375 high-risk couples contacted by telephone, 89.6% married each other, despite the known high-risk status. CONCLUSIONS The results showed excellent access to the target population. However, the program's objective of decreasing high-risk marriages was not as successful, indicating the need for improvement of health education programs for the public, more efforts in counseling high risk couples, and changes in the strategy of timing of screening in relation to marriage.