Objective. A retrospective study was conducted to explore the role and clinical value of optimized fetal main pulmonary artery Doppler parameters in the diagnosis and prognosis monitoring of neonatal respiratory distress syndrome (NRDS). Methods. Pregnant women admitted to our hospital for delivery from March 2019 to June 2021 were included in the study. There were 372 singleton pregnant women who voluntarily underwent ultrasound and Doppler examinations with informed consent for the study. The AT/ET ratio of the middle segment of the main pulmonary artery, the middle part of the left (or right) pulmonary artery, and the proximal segment of the intrapulmonary artery was measured by ultrasonic Doppler. According to the outcome of the newborn, it was divided into NRDS group ( n  =90) and non-NRDS group ( n  =282) to compare the differences of fetal AT/ET ratio at three Doppler sampling locations and the differences of fetal AT/ET ratio in different gestational weeks. Using Pearson’s correlation analysis, the correlation among the Doppler parameters of fetal main pulmonary artery, the ratio of AT and AT/ET, gestational weeks, and the efficiency of prenatal prediction of NRDS was evaluated by receiver-operating characteristic (ROC). In addition, the diagnostic efficiency of fetal main pulmonary artery Doppler parameter AT/ET ratio and amniotic fluid method for prenatal prediction of NRDS was compared. Results. Compared with the non-NRDS group, the gestational age, gestational age at delivery, and birth weight in the NRDS group were significantly lower than those in the non-NRDS group. The 1 min Apgar score of newborns was less than 7, and the proportion of newborns transferred to NICU was significantly higher than that in the control group. Compared with non-NRDS group, AT was significantly shortened, AT/ET ratio was significantly decreased, and ET was significantly prolonged in NRDS group. The fetal aortic blood flow parameters AT, ET, and AT/ET ratio in different gestational weeks were significantly different among the three groups. The AT/ET ratio in the middle segment of the aorta in NRDS group was lower than that in non-NRDS group. The ratio of AT/ET was still correlated with the occurrence of postpartum NRDS. The AUC value of NRDS predicted by AT/ET ratio was 0.984. In the combined determination of amniotic fluid Lh and S ratio and PG, the diagnostic accuracy of prenatal prediction of neonatal respiratory distress syndrome was 100.005%, 98.43%, and 95.56%, respectively. The accuracy of fetal aortic AT/ET ratio in prenatal prediction of neonatal respiratory distress syndrome was 100.005%, 95.28%, and 95.57%, respectively. The order of Kappa coefficient from high to low was amniotic fluid PG/L/S ratio, fetal main pulmonary artery blood flow parameter AT/ET ratio, amniotic fluid L/S ratio, OD650, amniotic fluid PG, and foam test. Conclusion. Fetal main pulmonary artery Doppler AT/ET ratio may be a very potential parameter for prenatal noninvasive prediction of NRDS. The fetal main pulmonary artery Doppler flow spectrum may be a very potential alternative to amniocentesis to evaluate FLM.