Context: Allogeneic hematopoietic stem cell transplantation (allo-HCT) with umbilical cord blood (UCB) is limited by the low number of hematopoietic stem cells. Omidubicel is an ex-vivo expanded stem cell product derived from UCB. Prospective clinical trials have demonstrated faster engraftment and fewer infections with omidubicel compared to UCB, but long-term outcomes are unknown. Objective: This is a pre-specified pooled secondary analysis of long-term outcomes with allo-HCT using omidubicel from 5 multicenter prospective trials. Design: Patients transplanted with omidubicel in one randomized phase III and four single-arm trials between 2006 and 2020 were followed for up to 10 years post-transplant. Setting: Twenty-six international academic transplant centers. Patients: Among 116 patients transplanted with either standalone omidubicel (n=92) or omidubicel with supplementary UCB (n=24), 97 (83.6%) engrafted with omidubicel, 11 (9.5%) with UCB, 2 mixed chimerism, 1 unevaluable, and 5 (4.3%) primary graft failure. This study included all patients aside from those engrafted with UCB (n=105). Median age was 42 (range, 2–62), 52.4% male, 30.5% non-white, and 30.5% high/very-high disease risk indices. Most common diseases were AML (40.1%), ALL (26.7%), MDS (13.3%), and sickle cell disease (7.6%). Results: Median follow-up was 22.0 months (range, 0.3–122.5). The 3-year OS and DFS were 62.5% (95%CI, 53.4–73.2) and 56.2% (95%CI, 47.0–67.1), respectively. Common causes of death included disease relapse (n=16) and infection (n=11). Three-year cumulative incidences of chronic GVHD and relapse were 37.8% (95%CI, 27.9–47.6) and 24.3% (95%CI, 16.1–33.3), respectively. Durable trilineage hematopoiesis was observed for up to 10 years. Similarly, median numbers of lymphoid subsets, including CD3+, CD4+, CD8+ T cells, CD19+ B cells, and CD16+/CD56+ NK cells were maintained within normal range for up to 8 years. Secondary graft failure was noted in 5 patients, 3 of whom underwent a second allo-HCT. Secondary hematologic malignancies included donor-derived myeloid neoplasm (dd-MN) (n=1; 40 months post-transplant) and PTLD (n=2; 17 and 20 months), with one death attributed to PTLD. Notably, there was also one case of dd-MN in the control UCB group of the phase III study. Conclusions: Omidubicel demonstrated durable long-term hematopoiesis and immune competence. One case of dd-MN was observed with both omidubicel and control UCB.