The objective of this study was to validate retrospective caregiver interviews for diagnosing major causes of severe neonatal illness and death. A convenience sample of 149 infants aged < 28 days with one or more suspected diagnoses of interest (low birthweight/severe malnutrition, preterm birth, birth asphyxia, birth trauma, neonatal tetanus, pneumonia, meningitis, septicaemia, diarrhoea, congenital malformation or injury) was taken from patients admitted to two hospitals in Dhaka, Bangladesh. Study paediatricians performed a standardised history and physical examination and ordered laboratory and radiographic tests according to study criteria. With a median interval of 64.5 days after death or hospital discharge, caregivers of 118 (79%) infants were interviewed about their child’s illness. Using reference diagnoses based on predefined clinical and laboratory criteria, the sensitivity and specificity of particular combinations of signs (algorithms) reported by the caregivers were ascertained. Sufficient numbers of children with five reference standard diagnoses were studied to validate caregiver reports. Algorithms with sensitivity and specificity > 80% were identified for neonatal tetanus, low birthweight/severe malnutrition and preterm delivery. Algorithms with specificities > 80% for birth asphyxia and pneumonia had sensitivities < 70%, or alternatively had high sensitivity with lower specificity. In settings with limited access to medical care, retrospective caregiver interviews provide a valid means of diagnosing several of the most common causes of severe neonatal illness and death.