Background and aims <p>To compare the efficacy and safety of different treatment regimens for decompensated liver cirrhosis (DLC), focusing on the novel method of endoscopic ultrasound (EUS)-guided intraportal autologous bone marrow transplantation (ABMT).</p> Methods <p>In this study, 65 DLC patients were assigned to one of three groups: EUS-POV ABMT (<i>n</i> = 22), PEV ABMT (<i>n</i> = 20), or conventional treatment (<i>n</i> = 23), and followed for 12 months. An exploratory analysis investigated the impact of graft quality (CD34 + cell proportion) on outcomes in the ABMT cohort.</p> Results <p>The EUS-POV group and PEV group that received ABMT showed different degrees of improvement in routine blood tests, transaminases, albumin levels, Child-Pugh scores, and coagulation function compared with the conventional treatment group, the clinical symptoms were relieved, with no apparent adverse reactions. The EUS-POV group was more effective than the PEV group in improving albumin levels and activated partial thromboplastin time (<i>P</i> &lt; 0.05); notably, histopathological improvement was observed in the EUS-POV group. An exploratory subgroup analysis based on CD34 + cell proportion (dichotomized by an ROC-derived cutoff) did not reveal a significant difference in the trajectory of liver function improvement between high and low CD34 groups. Importantly, linear mixed-model analysis revealed that the transplantation route, not the CD34 + cell proportion, was the primary factor associated with therapeutic efficacy (Interaction effect: <i>P</i> = 0.936).</p> Conclusions <p>EUS-guided intraportal ABMT is a safe and highly effective treatment for DLC, demonstrating clear advantages over peripheral infusion due to superior targeting and sustained clinical benefits. The success of ABMT appears to be influenced more critically by the cell delivery route than by the progenitor cell content of the graft.</p>