Thalassemia is one of the genetic diseases for which there are only a few successful prevention protocols. In this study, we aimed to analyze data for thalassemia newborns in a period of 6 years to find out the geographical distribution of cases, the “high-risk” provinces in Iran, the causes of thalassemia newborn cases, the coverage rate of the prevention programs and the limitations of the thalassemia registration system.To further our aim, an analytic cross-sectional study was designed at the Iranian Blood Transfusion Organization (IBTO), Tehran, Iran. A questionnaire was then prepared to gather data from each of the 30 provincial centers to find out the number and causes of thalassemia births. Furthermore, another questionnaire, to be completed by the physicians in charge, was aimed at gathering data from all 207 thalassemia care centers. We then performed a stratified analysis of the frequency of distributions; the associations among the existing variables were evaluated using the χ2 or Fisher’s exact tests at a 5.0% significance level.According to the findings, from 2001–2006, a total of 2091 thalassemia patients were born. The main causes were: the at-risk couples not using prenatal diagnosis (PND), marriages before the commencement of Iranian prevention plans, unregistered marriages based on religious conventions, among foreign citizens and the existence of some test errors. The causes of birth for 284 (13.6%) of new cases were not documented. There was a statistically significant difference between the five high-risk provinces regarding the proportional causes of thalassemia newborns [Pearson χ2 = 4.549; degree of freedom (df) = 8, p value = 0.0001].Although the plan succeeded in avoiding the annual birth of 826 new cases on average, there is continuing concern that more than 300 new cases were born every year during 2001–2006 and new prevention strategies need to be put into practice. It is highly recommended that focus be put on factors persistently causing the birth of new cases, especially in high-risk areas in which the success rates are lower than 50.0%.