Background Variable rates of malignancy and early infection have previously been reported in heart transplant (HTx) recipients who received induction therapy. This study hypothesized that induced pediatric patients would have an increased risk of these events compared with non-induced patients. Methods Data from a prospective, multicenter event-driven registry of outcomes after HTx listing in patients aged < 18 years was used to analyze risks of infection and malignancy and their association with induction between January 1993 and December 2007. Results Of 2,374 patients, 1,258 (53%) received induction and more frequently from 1999 to 2008 compared with 1993 to 1998 (70.8% vs 57.5%, p < 0.001). At HTx, induced patients were more likely to have congenital heart disease (56.9% vs 48.1%, p < 0.001) but no more likely to be positive for Epstein-Barr virus (50.3% vs 51.4%, p = 0.67). Post-transplant lymphoproliferative disease (PTLD) was the most common malignancy (n = 92) within 5 years of HTx. Patients who received induction had a lower risk for PTLD (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.30.84; p = 0.009) and early fungal infections (HR, 0.60; 91% CI, 0.400.91; p = 0.016). Among induction agents used, OKT3 was associated with lowest freedom from PTLD and fungal/cytomegalovirus infection. Conclusions Induction use has increased since 1999 and has not been associated with an increased risk of malignancy (predominantly PTLD) or overall infection. Because these adverse events occurred with higher rates in non-induced patients, it is likely that induction alone is not the primary risk determinant for PTLD and infection.