Background. The dosing intensity of antithymocyte globulin as induction therapy in heart transplantation remains controversial. We sought to evaluate the efficacy and safety of rabbit antithymocyte globulin at a total dose of 4.5 mg/kg compared with <4.5 mg/kg. Methods. This was a retrospective study of consecutive patients who underwent heart transplantation from January 2016 to December 2018 at a single quaternary care center. Exposure was defined as full antithymocyte globulin (4.5 mg/kg total) induction compared with partial (<4.5 mg/kg) induction. The primary outcome was the incidence of The International Society for Heart and Lung Transplantation 1990 acute cellular rejection grade 2 or above at 2 y. Secondary outcomes were all-cause mortality, number of infections, and time to therapeutic tacrolimus levels. Cox proportional hazard models were used to compare rejection rates and mortality. Results. Of 201 patients, 61 received partial and 140 received full induction. There was no difference in the cumulative incidence of cellular rejection grade 2 or above (18% versus 11.4%, P = 0.209) within 2 y. The adjusted hazard ratio was 1.45 (confidence interval: 0.62-3.37, P = 0.388) for partial compared with full induction for any grade rejection. Landmark survival analysis conditional on survival to 1 mo showed no difference in mortality (P = 0.239). There was no difference in the incidence of infection within 3 mo of transplant (partial 29.5% versus full 20.0%, P = 0.140). Both groups achieved therapeutic tacrolimus levels by day 7 after initiation. Conclusions. There was no difference in overall risk for any grade cellular rejection between partial or full dose induction therapy. Additionally, there was no difference in medium-term mortality from landmark survival analysis.