Background: Our pediatric heart transplant center transitioned from post-bypass basiliximab (BAS) induction to either anti-thymocyte globulin (ATG) or pre-bypass BAS. The purpose of this study was to compare first-year rejection rates before and after this change. Methods: A single-center retrospective analysis was conducted of pediatric heart transplant recipients from 2010 to 2019. Primary outcome was first-year rejection. Bivariate analysis, Kaplan-Meier curves, and multivariable regression were performed across eras. Results: Forty-three early era patients (55%) received post-bypass BAS, and 35 late era patients (45%) received pre-bypass BAS (n = 17) or ATG (n = 18). First-year rejection decreased in the late era (31% vs 53%, p =.05). This finding was more pronounced after excluding infants (38% vs 73%, p =.006). Late era was associated with a decreased likelihood of rejection (all cohort OR 0.19, 95% CI 0.05-0.66; infants excluded OR 0.17, 95% CI 0.04-0.61). No differences in post-transplant lymphoproliferative disease, donor-specific antibody, or infection were observed. Conclusions: Fewer late era patients receiving ATG or pre-bypass BAS induction had first-year rejection compared to the early era patients receiving standard post-bypass BAS induction. This programmatic shift in induction strategy was readily achievable and potentially effective in reducing first-year rejection.