ABO‐i heart transplantation can be performed in infants with end‐stage heart failure to increase organ availability. The development of newly detected DSAs is associated with decreased cardiac graft survival, and the effect of ABO‐i transplantation on DSA production is unknown. We examined DSA production and rejection frequency in infant recipients of ABO‐i and ABO‐c heart transplants via a retrospective cohort study of infant heart transplant recipients transplanted at a single pediatric center between January 2004 and November 2014. Patients were included if they were less than 1 year of age at transplant and had a minimum of 6 months follow‐up. DSA positivity was examined under two categories, either the lowest level detectable (MFI > 500) or a level presumed to have clinical relevance in our immunogenetics laboratory (MFI > 5000). Of 52 patients, 36 received ABO‐c transplants and 16 received ABO‐i transplants. Compared to ABO‐c recipients, the ABO‐i group showed a consistent but statistically non‐significant finding of less frequent ndDSA positivity (69.4% ABO‐c vs 43.8% ABO‐i with MFI >500, P = 0.122; 41.7% ABO‐c vs 25% ABO‐i with MFI >5000, P = 0.353). Additionally, ABO‐i patients were less likely to have any form of rejection (12.5% vs 47.2%, P = 0.027) or acute cellular rejection (6.3% vs 38.9%, P = 0.021). Our data suggest that infants receiving ABO‐i heart transplants may be less likely to develop ndDSAs or have rejection compared to same age ABO‐c recipients. Larger multicenter studies are needed to confirm results from this single center study.