Introduction We investigated the association of HLA on clinical outcomes in our cohort of patients in the haplo-HSCT program using the HLAMatchmaker (EM) and PIRCHE score (PS) algorithms. Methods The group comprised 64 patients (male = 35–54.7%, female 29– 45.3% ; median age 43 years) and their related haplo- HSCT donors (male = 30–46.9%, female 34–53.1%). HLA- A/B/C/DRB1/DQB1/DPB1 loci were analyzed. Results Multivariate analysis of the association between different HLA or patient/donor-related parameters and clinical outcome revealed the following associations with statistical significance: GvHD and HLA class I PS in the GvH direction (p = .0420) and relapse with diagnosis (p = .0163). For OS, the only variable showing a tendency of association was the source of HSCT (p = .0965). Conclusion Combined results of univariate and multivariate analysis suggest that the patients awaiting the selection of the best haplo- HSCT donor could benefit the most from the combination of all three approaches, in cases when a suitable donor can be chosen from a number of potential donors.