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Children with major and severe congenital heart disease (CHD) undergoing noncardiac surgery are at increased risk of mortality. The objective of this study was to identify the predictors for in-hospital mortality, and to develop a risk stratification score that could be used to help decision making and the development of perioperative management guidelines.We included all children with major (eg, tetralogy of Fallot with wide open pulmonary insufficiency, hypoplastic left heart syndrome including stage 1 repair) or severe CHD (eg, children with uncorrected CHD, children with documented pulmonary hypertension, children with ventricular dysfunction requiring medications, or children listed for heart transplant) recorded in the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program Pediatric databases in a derivation cohort, and those recorded in the 2014 database in a validation cohort. The primary outcome variable for our analysis was the incidence of in-hospital mortality. We used univariable and multivariable logistic regression to determine the preoperative predictors for in-hospital mortality and designed the risk stratification score.Among the 183,423 children included in the 2012, 2013, and 2014 American College of Surgeons National Surgical Quality Improvement Program database, we included 4375 children with major or severe CHD in the derivation cohort (mortality: 4.7% [204/4375]) and 2869 in the validation cohort (morality: 4.0% [115/2869]). Eight preoperative predictors were retained in the final multivariable logistic regression model: emergency procedure (odds ratio [OR]: 1.66, 95% confidence interval [CI]: 1.19–2.31, P = .003), severe CHD (OR: 1.65, 95% CI: 1.15–2.39, P = .007), single-ventricle physiology (OR: 1.83, 95% CI: 1.10–3.06, P = .020), previous surgery within 30 days (OR: 2.01, 95% CI: 1.40–2.89, P < .001), inotropic support (OR: 2.05, 95% CI: 1.40–3.01, P < .001), preoperative cardiopulmonary resuscitation (OR: 2.46, 95% CI: 1.32–4.57, P < .004), acute or chronic kidney injury (OR: 4.42, 95% CI: 2.00–9.75, P < .001), and mechanical ventilation (OR: 7.80, 95% CI: 5.42–11.21, P < .001). We created a risk stratification score ranging from 0 to 10 that showed very good calibration and discrimination in the validation cohort (area under the curve: 0.831 [95% CI: 0.787–0.875]), corresponding to an optimism-corrected area of 0.826. Scores ≤ 3 are associated with low risk of mortality (OR: 1.54, 95% CI: 0.78–3.04), scores ranging from 4 to 6 associated with medium risk (OR: 4.19, 95% CI: 2.56–6.87), and scores ≥ 7 associated with high risk (OR: 22.15, 95% CI: 15.06–32.59).Our study demonstrates that, in addition to preoperative markers of critical illness (eg, inotropic support, mechanical ventilation, preoperative cardiopulmonary resuscitation, and acute or chronic kidney injury), the type of lesion (eg, single-ventricle physiology) and the functional severity of the heart disease (eg, severe CHD) are strong predictors of in-hospital mortality in children undergoing noncardiac surgery.