Background: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potential cure for many hematologic cancers. Graft-versus-host disease (GVHD) is a significant cause of mortality after allo-HCT. Post-transplant cyclophosphamide (PTCy) in haploidentical HCT (haplo-HCT) has yielded survival outcomes similar to those seen in HLA-matched allo-HCT. Single center studies have demonstrated lower rates of chronic GVHD with the use of PTCy in HLA-matched allo-HCT. In this single center study, we analyzed the outcomes of HLA-matched and haplo-HCT in patients (pts) who received PTCy for GVHD ppx. Methods: Pts who received allo-HCT from matched related (MRD), matched unrelated (MUD), and haploidentical donors (Haplo) from Jan 2016 to July 2021 were identified. Pts who did not receive PTCy were excluded. Pts were divided into two groups – MRD/MUD and Haplo. Primary endpoint was cumulative incidence of chronic GVHD. Secondary endpoints were cumulative incidence of relapse, non-relapse mortality (NRM), and overall survival (OS) at 2-years. Comparisons were made based on log-rank test and a model for subhazard function of a failure event of primary interest with p < 0.05 used as cut-off point for statistical significance. Results: 62 pts (45 MRD/MUD,17 Haplo) were included. Baseline characteristics were similar. Median follow-up was 342 days post-transplant. Most had a diagnosis of AML (50%), high/very high DRI (48%), and received RIC (55%). Cumulative incidence of chronic GVHD was 11% overall (95% CI 5.8-21.3%); 6% for MRD/MUD and 27% for Haplo (p = 0.045). Cumulative incidence of relapse was 28% overall (95% CI 18-42%); 34% for MRD/MUD and 13% for Haplo (p = 0.09). Two-year OS was 55% overall (95% CI 39.1- 68.7%); 53% for MRD/MUD and 61% for Haplo (p = 0.043). There was no significant difference in incidence of grade 2-4 acute GVHD or NRM between groups. Conclusions: PTCy resulted in a significantly lower incidence of chronic GVHD in MRD/MUD group compared to Haplo group. Although cumulative incidence of relapse was not statistically different between groups, OS was worse in the MRD/MUD allo-HCT group after PTCy and most deaths were due to relapse.