<h3>Purpose</h3> The development of de novo donor-specific anti-HLA antibodies (DSA) is associated with worse outcomes in lung transplant recipients (LTxR). The purpose of this study is to evaluate IVIG monotherapy for de novo DSA in the absence of allograft dysfunction or clinical antibody-mediated rejection (AMR). <h3>Methods</h3> Adult LTxR between 2/2013 and 3/2021 treated with IVIG monotherapy for de novo DSA with no evidence of AMR were included. IVIG was initiated at 2g/kg followed by 1g/kg monthly for a minimum of 3 months or until clearance (up to 6 months). HLA Ab is routinely checked by Luminex SAB post-transplant at day 14, months 1, 3, 6, 9, 12, and 18, and monthly during IVIG treatment. Primary outcome was change in DSA after IVIG therapy. DSA clearance was defined as sum MFI less than 1000. <h3>Results</h3> 32 LTxR developed de novo DSA at a median of 33 days (18,143) post-transplant and were treated with IVIG. Mean follow-up time was 1330 days (861-1910). The median sum MFI for DSA at baseline was 4782 (2927,7490). DQ was the immunodominant DSA in 24 (75%) and only 2 (6%) patients had isolated class I DSA. MFI of sum DSA decreased by a median of 2993 (2051, 6358) after IVIG therapy; p < 0.0001. Eighteen (56%) cleared de novo DSA (Group 1) versus 14 (44%) did not clear (Group 2) at the end of IVIG therapy. There was no significant difference in age, gender, race, transplant indication or type, cPRA, HLA mismatch, or PGD. ACR and AMR tended to be more frequent in Group 2; ACR: 92.9% vs 61.1%, p=0.053; and AMR: 35.7% vs 5.6%, p=0.063. Overall survival for the entire cohort at 1, 3 and 5 years was 100%, 86%, 60%, respectively. There was no significant difference in chronic lung allograft dysfunction (CLAD) or survival between Groups (Table 1). <h3>Conclusion</h3> In LTxR, IVIG monotherapy is associated with significant reduction in de novo DSA. DSA clearance may result in less acute rejection. Randomized controlled trials are needed to determine the optimal strategy for managing de novo DSA.