Sensitized patients awaiting heart transplantation (HTx) are at increased risk for mortality as their waitlist time is lengthened due to incompatible donors and a subsequently narrowed donor pool. Therefore, these patients undergo desensitization therapies to lower circulating antibodies and to restore the donor pool for these patients. These patients subsequently undergo HTx; however it has not been well established as to their longer-term outcome following HTx. Between 2010 and 2014 we assessed 42 patients awaiting HTx who were sensitized (average cPRA 84%) and subsequently underwent desensitization therapy prior to HTx. These patients then underwent HTx and were followed for 5-year outcome. Endpoints post-HTx included 5-year survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, stroke), and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR)). Patients were compared to a contemporaneous group of HTx patients that did not receive desensitization therapy prior to HTx conditional to 1-year survival (n=329) for the same endpoints. Sensitized patients that received desensitization therapy prior to HTx had significantly lower freedom from AMR. There is a trend for increased freedom from NF-MACE in this desensitized group. There were no differences between the two groups in terms of survival, freedom from CAV, and freedom from ACR. Sensitized patients awaiting HTx who undergo desensitization therapy appear to have decreased freedom from first-year AMR. However, these patients appear to have comparable outcome (ie survival and CAV) at 5-years post-HTx to HTx patients that do not undergo desensitization therapy.