Late relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010 and December 31, 2016, considering data from the French national retrospective register ProMISe (SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy)). We included patients presenting LR, defined as a relapse occurring at least two years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, 7,582 AHSCT were performed in 29 centers and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered as LR, representing an incidence of 4.2% from the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia, and 40 (13.8%) with acute lymphoid leukemia. Median delay from AHSCT to LR was 38.2 months (29.2-49.7) and 27.2% of patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (5.6-46.4). The most common salvage therapy was induction regimen (55.5%), with complete remission being obtained for 50.7%. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (7.1-49.1). Non-relapse mortality after second AHSCT was 18.2%. We identified in the Cox model some of the associated factors with delay of LR: the disease status not in first complete remission at first HSCT (odds ratio (OR) 1.31, 1.04-1.64, p=0.02) and the use of post-transplant cyclophosphamide (OR 2.23, 1.21-4.14, p=0.01). Chronic GVHD appeared to be a protective factor (OR 0.64, 0.42-0.96, p=0.04). Prognosis of LR is better than early relapses, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity.