In the setting of haploidentical haematopoietic cell transplantation (HCT), post-transplant cyclophosphamide (PTCy) has dramatically reduced the incidence of graft-versus-host disease (GVHD) and non-relapse mortality. To further reduce GVHD incidence, the addition of antithymocyte globulin (ATG) to PTCy was evaluated in retrospective and non-comparative prospective studies showing promising results. We conducted a large retrospective analysis of the European Society for Blood and Marrow Transplantation (EBMT) registry to evaluate this approach. We analysed haploHCT with peripheral blood stem cells performed for haematological malignancies between 2014 and 2021. GVHD prophylaxis included either PTCy alone or PTCy+ATG. Four thousand five hundred and nineteen patients were analysed in the PTCy only group versus 675 with PTCy+ATG. Median follow-up was 29.80 months. In univariate analysis, 2-year GVHD-free, relapse-free survival (GRFS), relapse-free survival (RFS), overall survival (OS), cumulative incidence of relapse, non-relapse mortality (NRM) and chronic GvHD (cGVHD) were, respectively: 40.5% versus 37.5% (p = 0.098), 50.9% versus. 45.8% (p = 0.015), 56.9% versus 52.5% (p = 0.01), 24.2% versus 28.1% (p = 0.032), 25% versus 26.1% (p = 0.49) and 28.4% versus 18.5% (p < 0.001). aGVHD did not differ. After multivariable adjustment, OS and RFS were lower in the PTCy+ATG group: HR = 1.18 (p = 0.037) and HR = 1.18 (p = 0.027) and patients receiving PTCy+ATG had less cGVHD: HR = 0.68 (p = 0.004). In that retrospective analysis, the addition of ATG to PTCy for GVHD prophylaxis in haploHCT was associated with a reduction of cGVHD but also a worse OS and RFS.