Introduction & Objective: Congenital abnormalities are of the main causes of death and disability in children, infants and neonates in most countries in the world where a remarkable part of these disorders can be prevented with timely measures. The aim of this study was to provide the epidemiological characteristics of congenital anomalies in Iran. Materials & Methods: This cross sectional investigation was conducted on neonates of the birth year of 2016 in six major geographical regions in Iran including Tehran (capital), East Azerbaijan (northwest), Isfahan (center), Khuzestan (southwest), Sistan and Baluchistan (southeast) and Fars (south) Iran. Congenital defects were classified according to the coding system of the International Classification of Diseases (ICD_10). The sources of ascertainment of congenital defects were records of the cases diagnosed with birth defects, and hospital discharge forms. Fully trained and supervised data officers including midwives, nurses and medical coders were assigned to collect and management of the data for this investigation. Results: The prevalence of congenital anomalies in Tehran was estimated at 163.2, East Azerbaijan 356.4, Isfahan 326.0, Khuzestan 94.3, Sistan and Baluchistan 264.1, and Fars 376.0 per 10,000 births. The prevalence of major defect groups of genital organs, limb anomalies and heart defects were ranked the first, second and third, respectively, in the country. Hydrocele, undescended testicle and club-foot were the most common anomalies diagnosed in the organs in the study regions. Conclusions: Congenital anomalies are considerably prevalent in Iran, and it is estimated more than 100.000 cases of birth defects occur annually in the country. It seems, therefore, necessary to develop and implement new methods of screening procedures before, during and after birth to avoid occurring congenital anomalies in the country.