In the past decade, neonatal special care services in China have been established, during which time various therapies for neonatal respiratory failure have been introduced. The objective of this study was to investigate the incidence, management, outcome, and cost of neonatal respiratory failure treated by mechanical ventilation in 23 tertiary NICUs of major hospitals in southeastern and midwestern China. Data were collected over 12 consecutive months from 2004 to 2005 for neonates with neonatal respiratory failure. Eligible infants were those who required endotracheal intubation and mechanical ventilation and/or nasal continuous positive airway pressure for at least 24 hours and infants who died within 24 hours of ventilation during their first 7 days of life. Data characterized demographics, antenatal and perinatal history, illness severity score, primary disease, respiratory care, complications, survival, and clinical burden. From a total of 13,070 NICU admissions, there were 1722 (13.2%) cases of neonatal respiratory failure with respiratory distress syndrome, pneumonia/sepsis, and meconium aspiration syndrome as major causes. For infants who survived until discharge, the median length of ventilation was 70 hours. Overall, in-hospital mortality for neonatal respiratory failure was 32.1%. Logistic regressions showed that lower gestational age, vaginal delivery, fetal distress before delivery, presence of a major anomaly, and high severity score in preterm infants were associated with an increased risk for death. In term and postterm infants, only the presence of a major anomaly and a high severity score were significant risk factors for death. Mean length and cost of stay in hospital were 19.2 +/- 14.6 days and 14,966 +/- 13,465 Yuan in the survivors. Neonatal respiratory failure in the NICU of the provincial cities of China has high mortality and cost that are linked to geographic variability, a male predominance, and low proportion of very preterm infants, characteristic of sociocultural confounding background.