Myelodysplastic/myeloproliferative overlap neoplasms (MDS/MPN) are rare hematological malignancies. We analyzed the outcomes of 75 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for MDS/MPN. Graft-versus-host disease (GvHD) prophylaxis included post-transplantation cyclophosphamide (PTCy) in 71% of patients, with 44 (59%) receiving a combination of anti-thymocyte globulin (ATG) and PTCy. The median follow-up was 44.4 months. Primary graft failure occurred in three patients (4%). The incidence of grade III-IV acute GvHD at day 100 was 13% (95% CI: 6-22). At 2 years, the incidence of moderate-severe chronic GvHD, non-relapse mortality (NRM), relapse, GvHD-free/relapse-free survival (GRFS), and overall survival (OS) was 31.7% (95% CI 20.7-43.2), 37.9% (26-49), 17.4% (95% CI: 10-27), 24.8% (95% CI: 15-36), and 51.6% (95% CI: 39-63), respectively. PTCy-based GvHD prophylaxis seemed to be associated with improved OS (HR: 0.5, 95% CI: 0.3-0.9, p = 0.03), NRM (HR: 0.4, 95% CI: 0.2-0.9, p = 0.03), and GRFS (HR: 0.5, 95% CI: 0.3-0.8, 0.009). On multivariable analysis, the use of the PTCy-containing regimen seemed to be associated with improved NRM (HR: 0.41; 95% CI: 0.2-0.8; p = 0.03), GRFS (HR: 0.47; 95% CI: 0.3-0.8; p = 0.009), and OS (HR: 0.49; 95% CI: 0.2-0.9; p = 0.03) without an increased risk of relapse.