There is minimal data in the literature on the impact of pre-formed HLA DPB1 Donor Specific Antibodies in heart transplant patients. Accurately assessing these antibodies and the risk they pose would hopefully broaden the donor pool available to this group of patients. We have reviewed a case of heart transplantation across strong C1q binding donor specific antibody (DSA) to the HLA DP epitopes 84DEAV and 96K2. A 64y/o female with a history of breast cancer (1997), coronary artery disease, hypertension, hyperlipidemia (2002), presented with congestive heart failure. Sensitization history includes two children but no transfusions prior to transplant evaluation. Her initial HLA antibody results were reported as 0% cPRA for Class I and Class II (Luminex Single Antigen). There were HLA-DP antibodies present below the reporting cutoff ( 10,000 MFI). Antibody testing was done 10 days post LVAD implantation. Unfortunately, her cPRA levels increased dramatically (to 70% Class I and 48% Class II). The Class II antibodies were largely HLA-DP, likely to the 84DEAV and 96 K epitopes. Epitope analysis was initially performed using the HLA-DPB Compatability Wizard. The patient received a heart offer. Virtual crossmatch revealed a single DSA (Anti-DP10 > 20,000 MFI). A prospective CDC crossmatch was performed and was negative. The patient’s auto crossmatch was also negative. The patient was transplanted with this donor. A retrospective flow crossmatch was performed with pronase treated cells. It was T-cell negative, B-cell positive. Due to the positive flow crossmatch, the heart team performed one session of PP/IVIG on POD 1. This case provides insight to the role of high level C1q binding pre-formed donor specific HLA-DPB antibody, where the antibody is not confounded by additional DSA to other loci. It supports the concept that pre-existing HLA-DP antibodies may not represent a significant barrier to transplantation.