This study evaluates the feasibility of using post‐transplant cyclophosphamide (PTCY) prophylaxis in allo‐hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft‐versus‐host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty‐seven adults aged 65 or older with hematological malignancies, undergoing their first allo‐HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II–IV and III–IV acute GVHD, and the 2‐year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2‐year overall survival, non‐relapse mortality, cumulative incidence of relapse, and GVHD‐free relapse‐free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65–69. This study confirms the safety and feasibility of PTCY‐based allo‐HCT in older adults.