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Primary graft dysfunction (PGD) is seen in 7-29% of heart transplant (HTx) patients. Many of these patients with PGD also develop significant vasoplegia which requires high doses of intravenous vasoconstrictors. Outcomes of these patients with severe PGD is compromised within 30 days after HTx. Risk factors for the development of severe PGD have included angiotensin-converting enzyme inhibitors (ACEi). There may be a connection between ACEi and the kallikrein-kinin system whereby bradykinin is increased, thus resulting in more vasoplegia and PGD. It is not known whether the new drug, sacubitril/valsartan (S/V), is also a risk factor for the development of vasoplegia/severe PGD as bradykinin is also increased with sacubitril. Therefore, we reviewed our large HTx program to see if there is a correlation with S/V as a risk factor for this complication. Between 2015 and 2020, we assessed 65 HTx patients who were on S/V at the time of transplantation. Vasoplegia was defined as requiring more than 2 vasoconstricting drugs with systolic blood pressure still <90 mmHg. PGD was defined as per the ISHLT classification scheme (within 24 hours post-transplant). These patients on S/V were compared to patients on ACEi/ARB (1:1 control for age, sex, transplant year). Outcomes included survival, freedom from cardiac dysfunction, and freedom from non-fatal major adverse cardiac events in the first year after HTx. Compared to ACEi/ARB, S/V had similar risk for the development of vasoplegia or severe PGD. Furthermore, 1-year survival, freedom from cardiac dysfunction, and freedom from NF-MACE were not significantly different between groups. (see table) Patients undergoing HTx on S/V do not appear to be at risk for vasoplegia or severe PGD. [ABSTRACT FROM AUTHOR]