【Objective】 To investigate the main effect factors associated with neonatal respiratory failure(NRF). 【Methods】 Total of 188 neonatals with NRF and 190 neonatals with non-NRF of NICU were selected in the same period. The data of NRF were analyzed with case-control study. 【Results】 Tweleve factors were proved to be statistically significant difference. including residence, mode of delivery, multiple pregnancy, premature birth, pregnancy disease, fetal distress, amniotic fluid aspiration, hypoxic-ischemic encephalopathy, birth asphyxia,respiratory distress syndrome, congenital heart disease, meconium aspiration syndrome. 【Conclusions】 Controlling these risk factors of NRF is of great practical significance to reducing the incidence and mortality of NRF.