Although neonatal mortality is gradually decreasing worldwide, 98% of neonatal deaths occur in low- and middle-income countries, where hospital care for sick and premature neonates is often unavailable. Médecins Sans Frontières managed eight specialised neonatal care units (SNCUs) at district level in low-resource and conflict-affected settings in seven countries to assess the performance of the MSF SNCU model across different settings in Africa and Southern Asia. The study also aimed to describe the set-up of eight SNCUs, neonate characteristics and clinical outcomes among neonates from 2012 to 2015. It was concluded that the standardised SNCU model was implemented across different contexts and showed in-patient outcomes within acceptable limits. Low-tech medical care for sick and premature neonates can and should be implemented at district hospital level in low-resource settings.