Background: Pediatric acute respiratory distress syndrome (PARDS) has a mortality rate of up to 75%, which can be up to 90% in high-risk patients. Even with the use of advanced ventilation strategies, mortality remains unacceptably high at 40%. Airway pressure release ventilation (APRV) mode is a new strategy in PARDS. Our aim was to evaluate whether use of APRV mode in severe PARDS was associated with reduced hospital mortality compared to other modes of ventilation. Methods: This was a retrospective comparative study using data from case files in a pediatric intensive care unit of a university-affiliated tertiary-care hospital. The study period (January 2014 to December 2019) covered three years before routine use of APRV mode to three years after its implementation. We compared severe PARDS patients in two groups: The APRV group (who received APRV as rescue therapy after failing protective ventilation); and The Non-APRV group, who received other modes of ventilation. Results: A total of 24 patients in each group were analyzed. Overall in-hospital mortality in the APRV group was 79% versus 91% in the Non-APRV group. In-hospital mortality was significantly lower in the APRV group (univariate analysis: hazard ratio [HR], 0.27; 95% CI, 0.14–0.52; P=0.001 and multivariate analysis: HR, 0.03; 95% CI, 0.005–0.17; P=0.001). Survival times were significantly longer in the APRV group (median time to death: 7.5 days in APRV vs. 4.3 days in non-APRV; P=0.001). Conclusions Use of rescue APRV mode in severe PARDS may yield lower mortality rates and longer survival times.