Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells have become the preferred source of hematopoietic stem cells. We compared the effectiveness of G-CSF and pegylated G-CSF (peg-G-CSF) for hematopoietic stem cell mobilization in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) donors, and evaluated the transplant outcomes. We conducted a matched retrospective cohort study. Donors mobilized with peg-G-CSF (n = 70) and G-CSF (n = 70). 140 consecutive patients diagnosed with acute leukemia who underwent haplo-HSCT were included in this study. The findings revealed that the peg-G-CSF cohort exhibited significantly elevated myeloid-derived suppressor cells (MDSCs) levels in their grafts when compared to the G-CSF cohort (P < 0.001). The 100-day cumulative incidence (CI) of grade III-IV acute graft-versus-host disease (GVHD) and 1-year CI of moderate-to-severe chronic GVHD were 4.3% vs 14.3 % (P = 0.047) and 11.2% vs 27.4 % (P = 0.023), in the peg-G-CSF group and G-CSF group. Patients reveiving mobilized stem cell with peg-G-CSF had a significantly greater likelihood of 1-year GVHD-free relapse-free survival (GRFS) compared to patients reveiving mobilized stem cell with G-CSF (74.9% vs 37.9 %, P < 0.001). The higher graft MDSCs proportion was associated with lower grade II-IV aGVHD, cGVHD (P < 0.05) and higher GRFS in the univariate analysis (P < 0.05). Multivariate analysis showed that MDSCs proportion higher than 11.36 % (HR, 0.305; 95 % CI, 0.154–0.606; P = 0.001) and peg-G-CSF for stem cell mobilization (HR, 0.466; 95 % CI, 0.251–0.865; P = 0.016) were independent prognostic factors of GRFS. The superior survival rates observed in recipients of peg-G-CSF-mobilized cells are likely due to reduced acute GVHD, potentially mediated by the increased MDSCs within the grafts.