Although overall outcomes have improved for single-ventricle patients, substantial morbidity and mortality remain for certain high-risk groups. The hybrid stage I procedure is an alternative to the Norwood operation for stage I palliation, but it remains unclear whether it is associated with improved outcomes in high-risk patients. This single-center, nested, case-control study included high-risk patients with a systemic right ventricle who underwent hybrid stage I or Norwood palliation from January 2000 to December 2016. High-risk features included prematurity < 34 weeks, birth weight < 2.5 kg, restrictive/intact atrial septum, at least moderate atrioventricular valve regurgitation or right ventricular dysfunction, genetic or extracardiac anomalies, or left ventricular sinusoids. Patients were matched by presence of genetic anomaly, restrictive/intact atrial septum, and prematurity/weight < 2 kg. Early and midterm outcomes were compared in the matched hybrid vs Norwood groups. The study included 96 patients (35 hybrid, 61 Norwood). Despite improved 30-day survival in hybrid patients (91% vs 66%, P < .01), 1-year survival was similar between the hybrid and Norwood groups (46% vs 48%, P= .9). No hybrid patients required dialysis or extracorporeal membrane oxygenation after stage I palliation as compared with 19% and 22% of Norwood patients, respectively (both P < .01). Hybrid patients, however, required more unplanned reinterventions (43% vs 21%, P= .02). There remains significant morbidity and mortality among high-risk single-ventricle infants. Despite an early survival benefit, hybrid stage I palliation has not been associated with improved midterm outcomes at our center.