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Although haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) has achieved similar survival to HLA-identical sibling donor (ISD) transplantation, the delayed hematopoietic engraftment as well as higher incidence of graft-versus-host-disease (GVHD), results in prolonged hospitalization, higher costs, and increased morbidity. In this study, a prospective, non-randomized clinical study was designed to evaluate the outcomes of patients who underwent HID HSCT supported by cord blood or ISD HSCT. Between May 2017 and November 2020, 113 patients were enrolled to undergo HID HSCT supported by cord blood (n=88) or ISD HSCT (n=25). The cumulative incidence of neutrophil and platelet engraftment at 30days was comparable in these two groups. Importantly, there was no significant difference in the cumulative incidence of grade II-IV aGVHD at 100days (20.5% [95% confidence interval [CI]: 12.2%–28.8%] versus 12.0% [95% CI: 0.2%–23.8%], P = 0.32) and cGVHD at 1 year (19.5% [95% CI: 11.2%–27.8%] versus 16.6% [[95% CI: 1.3%–31.9%] P = 0.70) between the two groups. Among the HID and ISD groups, the 2-year disease free survival was 76.8 and 80.0% ( P = 0.83), the 2-year overall survival was 82.4 and 88.0% ( P = 0.66), the 2-year GVHD-free, relapse-free survival was 68.9 and 75.3% ( P = 0.62), respectively. Our results indicate that HID transplantation supported by cord blood may offer a good alternative to ISD HSCT for patients with hematopoietic malignancies. Trial registration: Effect of co-infusion third party umbilical cord blood stem cells on haploidentical hematopoietic stem cell transplantation https://www.chictr.org.cn Reg. No. ChiCTR-OIN-17011426.