<h3>Purpose</h3> Among patients listed for heart transplantation (HT), human leukocyte antigen (HLA) sensitization is a major risk factor for prolonged wait-list time, wait-list mortality, and delisting. Desensitization therapies (Dx) like immunoglobulins (Ig), plasmapheresis and direct immunomodulators (IM)s such as B-cell depletion therapies (BCDT) or proteosome inhibitors (PI) have been used to reduce levels of sensitization. Specifically, for left ventricular assist device (LVAD) patients, however, Dx may pose unique problems: plasmapheresis removes coagulation factors and can increase bleeding risk, and IMs may worsen the risk of LVAD associated infections. We sought to assess safety and efficacy of Dx among LVAD patients. <h3>Methods</h3> LVAD patients undergoing Dx including plasmapheresis, Ig, Rituximab (BCDT) or Bortezomib (PI) were analyzed. Data on major coagulopathic and infectious complications while on LVAD support, changes in HLA antibodies and rates of HT were collected. Wilcoxon matched-pairs signed-ranks test was performed to compare changes in HLA antibody profiles following Dx. <h3>Results</h3> Between March 2016 and June 2021, 14 waitlisted LVAD patients underwent Dx [age: 52 years (inter-quartile range (IQR): 44, 60), 78% female, 43% Black, 64% HeartWare and 36% HeartMate III]. DTs were initiated 282 days (IQR: 129, 429) post LVAD implantation, with the majority receiving plasmapheresis (86%), Ig (86%) and bortezomib (93%). Two patients developed de-novo LVAD infections, and 2 suffered neurological events (1 hemorrhagic stroke and 1 transient ischemic event); no episodes of de-novo mucosal bleeding or hemolysis were noted. Eleven (78.6%) patients underwent HT, 2 remain waitlisted and 1 was delisted (myocardial recovery). Figure shows changes in antibody profiles with Dx. <h3>Conclusion</h3> In our cohort of highly sensitized LVAD patients, Dx were largely safe, significantly reduced class I panel reactive antibodies, and resulted in successful HT for most patients; future large scale trial data is necessary to validate our findings.