Objectives: The aim of this study was to demonstrate the effectiveness and safety of autologous hematopoietic stem cell transplantation in real-world clinical practice. Participants and methods: A retrospective study was conducted, collecting and analyzing medical data of all 28 participants who underwent autologous hematopoietic stem cell transplantation at the Department of Hematology, University Hospital of Split, from February 2021 to June 2023. Results: From the total number of participants, 20 had a diagnosis of multiple myeloma, 7 had lymphoma, and 1 patient had POEMS/Castelman's disease. The median follow-up period was 12.5 months. The overall response rate to therapy was 89.3%. Complete remission (CR) or very good partial remission (VGPR) was achieved in 95% of patients with multiple myeloma. Disease progression was observed in 4 (14.3%) participants. All transplanted patients were alive during the study period (OS rate = 100%). The median progression-free survival (PFS) was not reached, and the PFS rate after 24 months was 85.21%. Complications occurred in a total of 16 participants (57.1%), and febrile episodes were reported in 12 of them (42.9%). The median recovery time for neutrophils and platelets were 13 and 21 days respectively. All participants received platelet transfusion support, and 60% of them received red blood cell transfusion support. Conclusion: Autologous hematopoietic stem cell transplantation is an effective modality in the treatment of hematological patients, particularly those with multiple myeloma. The safety profile of this procedure is acceptable. The initial results of the Transplantation Center at University Hospital of Split are excellent and represent a significant advancement in the treatment of hematological patients outside Zagreb. Longer follow-up of participants is needed to provide a more comprehensive comparison of results in real-world clinical practice across different transplantation centers.