Background In shunt‐dependent, single‐ventricle patients, mortality remains high in the interstage period between discharge after neonatal surgery and stage 2 operation. We sought to evaluate the impact of our infant single‐ventricle management and monitoring program (ISVMP) on interstage mortality and stage 2 outcomes. Methods and Results This retrospective single‐center cohort study compared patients enrolled in ISVMP at hospital discharge with historical controls. The relationship of ISVMP to interstage mortality was determined with a bivariate probit model for the joint modeling of both groups, using an instrumental variables approach. We included 166 ISVMP participants (December 1, 2010, to June 30, 2015) and 168 controls (January 1, 2007, to November 30, 2010). The groups did not differ by anatomy, gender, race, or genetic syndrome. Mortality was lower in the ISVMP group (5.4%) versus controls (13%). An ISVMP infant compared with a historical control had an average 29% lower predicted probability of interstage death (adjusted probability: −0.29; 95% CI, −0.52 to −0.057; P=0.015). On stratified analysis, mortality was lower in the hypoplastic left heart syndrome subgroup undergoing Norwood operation (4/84 [4.8%] versus 12/90 [14%], P=0.03) but not in those with initial palliation of shunt only (P=0.90). ISVMP participants were younger at the time of the stage 2 operation (138 versus 160 days, P
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