Objective To study the clinical evaluation of gas exchange impairment in neonatal respiratory failure.Methods Blood gas, PaO2/PAO2, Qs/QT, PaO2/FiO2, A-aDO2 and RI of 53 newborn infants with respiratory failure in NICU of PUMCH from Jan. 1993 to Dec. 1997 were measured. Results These infants were divided into two groups according to PaO2/PAO2: moderate and severe respiratory failure. Qs/QT(11±3)%, PaO2/FiO2(183±113), A-aDO2(22.9±6.8)kPa, RI(2.5 ±0.8) in 21 neonates with moderate respiratory failure; Qs/QT(24±6)%, PaO2/FiO2 (82±30), A-aDO2 (49.3 ± 17.8)kPa,RI(7.6 ±3.4) in 32 neonates with severe respiratory failure(P＜0.001). These results in respiratory failure caused by different pathogenesis were different. In meconium aspiration and pneumothorax group there were the highestQs/QT(32±3)% ,A-aDO2 (69.8 ± 12.2)kPa,RI(9.2 ±2.9)and the lowest PaO2/FiO2 (77±39). Mortality of infants with high pulmonary shunt was high. Qs/QT(17±8)% in 38 survives and (24±6)% in 10 died neonates( P＜0.05). Conclusion The clinical evaluation using these indexes for newborn infants with respiratory failure is beneficial in recognizing pathogenesis,guiding therapy and evaluating prognosis.