Background: AL amyloidosis is plasma cell disorder involving irreversible deposition of amyloid fibrils, leading to end-organ damage. Treatment strategies include systemic therapy, autologous stem cell transplant (ASCT), and organ transplant. The ANDROMEDA trial established daratumumab (Dara) in combination with cyclophosphamide, bortezomib (Bor), and dexamethasone (CyBorD) as a new standard of care in newly diagnosed AL amyloidosis. Notably, only 2% of the trial population had stage IIIB cardiac disease by Mayo 2004 criteria. We present real world data of orthotopic heart transplantation (OHT) recipients with AL amyloidosis at our institution to understand the safety and outcomes of Dara use in the setting of advanced cardiac involvement. Methods: We performed a retrospective review of 9 patients at our institution who had received OHT since 2019 for AL amyloidosis. Demographics, disease details, treatment selection, response, and outcomes data were collected and described. Results: The cohort included 22% Black and 22% Hispanic patients, and the median age at diagnosis was 56. All patients had Revised Mayo stage 3 or 4 disease with advanced cardiac involvement requiring OHT. Patients had a median of 3 (2-4) suspected organs involved; none had symptomatic myeloma. Four patients received induction CyBorD; 2 achieved complete response (CR), 1 very good partial response (VGPR), and 1 partial response (PR) prior to OHT. Three of 4 received bridging therapy (Dara-Bor triplet or Bor alone) prior to ASCT, 2 due to inadequate response and 1 to maintain CR, and all achieved CR post-ASCT. Median time from OHT to ASCT was 13.5 months (range: 8-17), with bridging therapy starting at a median of 6 months post-OHT if received, with concomitant reduction in OHT immunosuppression. Five patients received DaraCyBorD induction: 2 achieved CR, 2 achieved VGPR, and 1 achieved PR prior to OHT. No patient who received DaraCyBorD received ASCT. Those not in CR received further therapy post-OHT. At the time of this analysis, 89% of patients remain in CR with 2 receiving ongoing therapy. All patients are alive with a median follow-up of 22 months (range: 11-35) since OHT without evidence for organ rejection. Conclusions: We demonstrate that the use of subcutaneous Dara is tolerable and effective in advanced stage cardiac AL amyloidosis, an underrepresented group in the literature. Patients who received DaraCyBorD followed by OHT without ASCT achieved similar outcomes to those who received CyBorD, OHT, and ASCT. The routine use of Dara may therefore negate the need for ASCT in this setting, given its favorable toxicity profile and reduced cost.