Abstract Background The neonatal mortality rate is 19 deaths per 1000 live births worldwide. Studies have shown that neonatal registry network systems can provide the necessary data for establishing evidence- based strategies to decrease the complications in high-risk neonates and consequently reduce neonatal mortality rate. Aim of the Work To determine the frequency and distribution of neonatal critical illnesses in Neonatal Intensive Care Unit (NICU) of Ain Shams University. Patients and Methods This descriptive study was conducted in NICU, Children's Hospital, Ain Shams University. The data collected from initiated neonatal registry through electronic medical record to reach sample size number (381) patients. The current study was conducted after approval by the Department of Pediatrics, and the local Ethics and Research Committee, Faculty of Medicine, Ain Shams University. Results The mean ± (SD) age at admission was 5.52 ± 6.9 days, gestational age was 36.19 ± 2.47 weeks, more than half of our patients were males (55.6%) and females represented in (44.4%). Two- thirds (64.2%) of our participants were full term, and preterm were only (35.7%). The main etiology of NICU admission was respiratory disease (35.7%), followed by neonatal sepsis (25.2%), neonatal jaundice (21%), congenital anomalies (12.3%), CNS diseases (6.8%), inborn errors of metabolism (1%) and mortality rate was 10.5%. Four cases had inborn errors of metabolism in the form of: Maple syrup urine disease (one case), organic academia (one cases) and 2 cases referred to genetic clinic for further assessment. Congenital heart diseases in our study was reported in (7.9%) of neonates. The main etiology among them was reported in following order: PDA / pulmonary hypertension (26.7%), VSD (13.3%), Fallot tetralogy (10%), transposition of great arteries (10%), supraventricular tachycardia (6.7%) then many etiologies represented in 3.3% as Ebstein anomaly, right single ventricle, heart block, pulmonary artery stenosis, arrhythmia, tricuspid atresia and left hypoplastic heart disease. Conclusion This study showed the ability of the electronic medical record to store large amounts of data which creates a potential for information overload in the intensive care (ICU) setting. This will stimulate and facilitate research on neonatal critical illness and its management, mortality and morbidity outcomes of neonates admitted to NICUs in Children's Hospital, Ain Shams University, Egypt.