The objective of the research was to establish the impact of diaphragm-protective mechanical ventilation on the rate of successful weaning from invasive and non-invasive mechanical ventilation in children with acute respiratory failure. We conducted a prospective, observational cohort study. Seventy-eight patients were randomly divided into 2 groups: patients of Group I received lung-protective mechanical ventilation; patients of group II received diaphragm-protective + lung-protective mechanical ventilation. For age-specific data analysis, patients were divided into age subgroups: the 1<^>st subgroup included children being 1 to 12 months old; the 2<^>nd age subgroup comprised children being 12 to 36 months old. We started respiratory support in both groups with invasive mechanical ventilation and when patients met the criteria, we weaned them. We confirmed successful weaning, when patients had no need to be mechanically ventilated within next 48 hours, otherwise, they were intubated again. Before the second trial to wean, patients in group I were simply extubated, while patients in group II received non-invasive mechanical ventilation. The primary endpoint was the rate of successful weaning from mechanical ventilation in the first trial. The secondary outcomes were complications, namely reintubation rate, tracheostomy rate and death. We found a significant difference in the primary outcome for the 1<^>st age subgroup: there were 72,4 % in Group I vs. 52,6 % in Group II successfully weaned patients (p = 0,04). No significant difference in the primary outcome was observed in the 2<^>nd age subgroup: there were 80 % in Group I vs. 82,3 % in Group II successfully weaned patients (p = 0,78). There were significant differences in the secondary outcomes between groups in the 1<^>st age subgroup, namely reintubation rate was seen in 9,1 % patients of group I vs. 36,8 % patients of group II (p = 0,05); death happened in 18,2 % cases in group I vs. no cases in group II (p = 0,01). There were no differences in tracheostomy rate in the 1st age subgroup and there were no differences in the secondary outcomes between groups in 2<^>nd age subgroup. Conclusions: diaphragm-protective mechanical ventilation significantly reduced the incidence of successful weaning from invasive mechanical ventilation; however, it increased the incidence of successful weaning from non-invasive mechanical ventilation, and, significantly decreased the mortality rate in the I<^>st age subgroup, while in the 2<^>nd age subgroup, it had no impact on the incidence of successful weaning from invasive mechanical ventilation and mortality rate.

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