A prior study showed lack of production of donor specific antibodies to HLA antigens (DSAs) in non-sensitized ABO-incompatible (ABO-i) and similar age ABO-compatible (ABO-c) recipients. We examined whether ABO compatibility has an effect on de novo DSA production in an American cohort regardless of pre-transplant sensitization status. A retrospective cohort study of recipients < 1 year of age at transplant with > 6 months of follow-up, transplanted between 1/2004-10/2013 at a single U.S. pediatric heart transplant center. Outcomes included development of DSAs and history of rejection. DSA positivity was defined as either the lowest level detectable by assay, mean fluorescence intensity (MFI) >500, or suggestive of clinical relevance, MFI>5000. Of 47 patients, 33 received ABO-c transplants and 14 received ABO-i transplants (median age 5.5 mo vs. 4.2 mo, p=0.577). Median duration of follow-up was 45 mo for ABO-c and 47 mo for ABO-i (p=0.745). There were no significant differences between the two groups in gender, cardiac diagnosis, prior open heart surgery, prior homograft, crossmatch, pre-transplant sensitization to anti-HLA antibodies, number of HLA mismatches, and immunosuppression regimen. Compared to ABO-c recipients, the ABO-i group consistently showed a trend of less frequent de novo DSA positivity and rejection (see Table). For the entire cohort, there was a significant association between antibody-mediated rejection and DSA positivity (36.8% in DSA-positive vs. 7.1% in DSA-negative using MFI>5000 as the cutoff, p=0.021; and 31% vs. 0% using MFI>500, p=0.008). A similar though not statistically significant trend was seen for cellular rejection. Our data suggest that patients receiving ABO-i heart transplants within the first year of life develop fewer DSAs compared to recipients of ABO-c transplants, which may lead to fewer rejections. Larger sample sizes with adjustment for covariates will be needed to confirm results from this pilot study.