Background: Neonatal deaths, especially among the Low Birth Weight (LBW) babies, are of major concern in the Neonatal intensive care unit of El-Kasr El-Aini hospital, Cairo University. Several instruments have been developed to predict initial mortality risk among the LBW babies. Among them is the Clinical Risk Index for Babies scoring system also known as CRIB II score.Objectives: The present study was done to assess the efficiency of CRIB II score as a tool to predict the risk for neonatal mortality among the LBW babies at El-Kasr El-Aini hospital.Patients and Methods: This is a prospective cohort study which was conducted on 113 neonates, who were admitted during the first 24 hours to the NICU of El-Kasr El-Aini hospital, Cairo University within the period of November 2013 till May 2014. They were subjected to detailed history taking, complete neonatal examination, arterial blood gas analysis and variables of CRIB II score. CRIB II score was applied for these neonates in the first day of admission. All subjects were followed up from admission till discharge or death, whichever came first.Results: Fifty eight cases (51.3%) were males and fifty five cases (48.7%) were females. The gestational age ranged from 25-32 weeks with a mean of 28.7 (± 2.1), the birth weight ranged from 700-1500 gm with a mean of 1134.5 (± 202). CRIB II score ranged from 1-19 with a mean of 9.9 (± 4.0). Total mortality was 34.5%. A statistically significant positive correlation was found between gestational age, birth weight, temprature, base excess and CRIB II score and mortality, the higher the CRIB II score the higher the mortality (P-value < 0.001). No significant differences between males and females regarding mortality, (P= 0.2). Progressive increase in mortality with increasing CRIB II score level; Mortality was 0 (0%), 2 (4.8%), 28 (68.3%) and 9 (100%) in level I, II, III and IV CRIB II score respectively. CRIB II score ≥ 11, gestational age ≤ 28 and birth weight ≤ 1100 were all found to be significantly associated with hospital neonatal mortality. Area under ROC curve for CRIB II, gestational age and birth weight were found to be (0.968, 0.900 and 0.834) respectively. CRIB II score with cut off point of ≥ 11 was found to be the most sensitive (94.9%) with the best predictive value (74.0%) and specificity (82.4%) compared to birthweight and gestational age. The highest Accuracy was obtained by CRIB II score (86.7%) followed by gestational age (81.4%) and birth weight (72.5%).CRIB II score showed good calibration to predict neonatal mortality when Hosmer-lemeshow of goodness of fit test was applied (P value = 0.952).Conclusion and Recommendation: CRIB II score is a valid tool of initial risk assessment even in extremely low birth weight infants in predicting hospital outcome more accurately than birth weight or gestational age alone. It is also found to be easily applicable and therefore should replace the traditional models as the predictor of neonatal outcome. Application of the CRIB II score should be done on admission of preterm babies to the NICU to identify high risk neonates in order to prioritise care for such neonates for better outcome.