OBJECTIVE: To study the effects of bifidobacterium on respiratory and gastrointestinal tracts in neonates receiving mechanical ventilation. METHODS: The eligible neonates were randomly assigned into two groups: observed (n=38) and control (n=43). The observed group was given bifidobacteria daily (one capsule per time, for 7 days) by nasal feeding from the next day after mechanical ventilation. Gastric pH, gastric bacteria colonization, feeding intolerance, weight gain, the incidence of ventilator-associated pneumonia (VAP), and the homology between the bacteria isolated from intra-gastric colonization with those causing VAP were observed. RESULTS: The incidence of gastric pH≤3 in the observed group was significantly higher than that in the control group 3, 5 and 7 days after mechanical ventilation (P＜0.01). The rate of gastric bacteria colonization in the observed group was significantly lower than that in the control group 5 and 7 days after mechanical ventilation (P＜0.01). The incidences of feeding intolerance and VAP in the observed group were significantly lower than those in the control group (P＜0.05, P＜0.01, respectively). The rate of homology of the bacteria isolated from intra-gastric colonization with those causing VAP in the observed group was significantly lower than that in the control group (P＜0.01). There were no significant differences in the weight gain between the two groups. CONCLUSIONS: Bifidobacterium can decrease gastric pH, gastric bacteria colonization and feeding intolerance, thus blocks the infection route "stomach-oropharynx-respiratory tract" indirectly and decreases the incidence of endogenous VAP in neonates receiving mechanical ventilation.