Objective To compare the safety and effectiveness of coaxial technique and non-coaxial technique in ultrasound-guided liver biopsy. Methods We retrospectively collected patient information from January 2012 to January 2024, who underwent ultrasound-guided liver biopsy at our hospital. The technique success rate, specimen adequacy rate, number of specimens obtained, specimen length, and incidence of complications were compared between the coaxial group and non-coaxial group. Results After screening, a total of 3358 patients were included, with 2568 in the coaxial group and 790 in the non-coaxial group. There was no significant difference between the two groups in terms of technique success rate, specimen adequacy rate, specimen length, or number of specimens obtained. The incidence rates of complications (6.39% vs. 10.51%, P=0.001) and bleeding (0.74% vs. 1.65%, P=0.046) were significantly lower in the coaxial group compared to the non-coaxial group. Conclusion Both coaxial technique and non-coaxial technique can provide sufficient tissue for pathological diagnosis after ultrasound-guided liver biopsy; however, coaxial technique offers higher safety.