Objective To explore the application effect of zero defect nursing based on multidisciplinary team (MDT) model in mechanically ventilated infants with neonatal respiratory distress syndrome (NRDS). Methods A total of 78 infants with NRDS who were admitted to Zhoukou Central Hospital for mechanical ventilation treatment from January 2022 to January 2024 were selected as the research subjects. They were randomly divided into a control group and an observation group using a random number table method, with 39 cases in each group. The control group received routine care, while the observation group received zero defect nursing based on MDT model on top of the control group. The perioperative indicators, oxygenation function and complications of the two groups were compared. Results The hospitalization time and mechanical ventilation time of the observation group were shorter than those of the control group, and the medical expenses and the frequency of pulmonary surfactant use were lower than those of the control group (P<0.05). After nursing, the arterial partial pressure of oxygen (PaO2) and arterial oxygen saturation (SaO2) in the observation group were higher than those in the control group, while the arterial partial pressure of carbon dioxide (PaCO2) and incidence of complications were lower than those in the control group (P <0.05). Conclusion The application effect of zero defect nursing based on MDT model for mechanically ventilated infants with NRDS is good, which can significantly improve the oxygenation function of infants, reduce the risk of complications, promote disease recovery, and thus improve perioperative indicators.