The study aimed primarily to evaluate the efficacy of noninvasive ventilation (NIV) and to identify possible predictors for success of NIV therapy in preventing extubation failure in critically ill children with heart disease. The secondary objectives of this study were to assess the efficacy of prophylactic NIV therapy initiated immediately after tracheal extubation and to determine the characteristics, outcomes, and complications associated with NIV therapy in pediatric cardiac patients. A retrospective review examined the medical records of all children between the ages 1 day and 18 years who sustained acute respiratory failure (ARF) that required NIV in the cardiovascular intensive care unit (CVICU) at Lucile Packard Children’s Hospital between January 2008 and June 2010. Patients were assigned to a prophylactic group if NIV was started directly after extubation and to a nonprophylactic group if NIV was started after signs and symptoms of ARF developed. Patients were designated as responders if they received NIV and did not require reintubation during their CVICU stay and nonresponders if they failed NIV and reintubation was performed. The data collected included demographic data, preexisting conditions, pre-event characteristics, event characteristics, and outcome data. The outcome data evaluated included success or failure of NIV, duration of NIV, CVICU length of stay (LOS), hospital LOS, and hospital mortality. The two complications of NIV assessed in the study included nasal bridge or forehead skin necrosis and pneumothorax. The 221 eligible events during the study period involved 172 responders (77.8 %) and 49 nonresponders (22.2 %). A total of 201 events experienced by the study cohort received continuous positive airway pressure (CPAP), with 156 responders (78 %), whereas 20 events received bilevel positive airway pressure (BiPAP), with 16 responders (80 %). In the study, 58 events (26.3 %) were assigned to the prophylactic group and 163 events (73.7 %) to the nonprophylactic group. Compared with the nonprophylactic group, the prophylactic group experienced significantly shorter CVICU LOS (median, 49 vs 88 days; p = 0.03) and hospital LOS (median, 60 vs 103 days; p = 0.05). The CVICU LOS and hospital LOS did not differ significantly between the responders (p = 0.56) and nonresponders (p = 0.88). Significant variables identifying a responder included a lower risk-adjusted classification for congenital heart surgery (RACHS-1) score (1–3), a good left ventricular ejection fraction, a normal respiratory rate (RR), normal or appropriate oxygen saturation, prophylactic or therapeutic glucocorticoid therapy within 24 h of NIV initiation, presence of atelectasis, fewer than two organ system dysfunctions, fewer days of intubation before extubation, no clinical or microbiologic evidence of sepsis, and no history of reactive airway disease. As a well-tolerated therapy, NIV can be safely and successfully applied in critically ill children with cardiac disease to prevent extubation failure. The independent predictors of NIV success include lower RACHS-1 classification, presence of atelectasis, steroid therapy received within 24 h after NIV, and normal heart rate and oxygen saturations demonstrated within 24 h after initiation of NIV.