Objective To explore the clinical effect of comprehensive nursing intervention in patients with mechanical ventilate associated pneumonia in respiratory intensive care unit. Methods From August 2020 to August 2022, 69 patients with mechanical ventilation in ICU who met the inclusion criteria were divided into control group and observation group by random number table, with 30 cases in each group. The control group received routine nursing intervention, and the observation group added comprehensive nursing intervention on the basis of the control group. The changes of CPIS score and clinical indexes before and after intervention were compared between the two groups. The prognosis of the two groups was observed. Results CPIS score in 2 groups after intervention was lower than before intervention, and observation group was lower than control group, the difference was statistically significant (P<0.05). All the clinical indexes in both groups were better after intervention than before intervention, and the observation group was better than the control group, the difference was statistically significant (P<0.05). The incidence of mechanical ventilation-associated pneumonia in the observation group was lower than that in the control group, and the hospitalization was better than that in the control group, the difference was statistically significant (P<0.05). Conclusion For ICU patients with mechanical ventilator-associated pneumonia, comprehensive nursing intervention can improve the blood gas analysis index of patients, reduce the probability of mechanical ventilator-associated pneumonia, and facilitate the prognosis.