Background: Liver biopsy is the gold standard method for the assessment of liver fibrosis and diagnosis of different liver diseases. The most common method of liver biopsy is transdermal biopsy, which can be performed under the guidance of ultrasound (US) or blindly. The present study aimed at comparing the success rate and complications of these two methods in patients undergoing liver biopsy. Materials and Methods: This interventional study was performed on 102 patients, who were candidates for liver biopsy without any contraindications. The patients were randomly divided in two groups of US-guided biopsy and blind biopsy. The patients’ demographics, indications for biopsy, and complications were collected in a checklist. Data were analyzed using Chi-square test and independent sample t-test in SPSS version 16. Results: Among 102 participants, 51 patients (25 males and 26 females), with the mean age of 39. 69 ± 12. 93 years, underwent US-guided biopsy, while 51 patients (29 males and 26 female), with the mean age of 39. 65 ± 13. 73 years, underwent blind biopsy. Liver biopsy was successful in 88. 2% of the patients in both groups. The most common complication was reduced hemoglobin level, which was not significantly different between the groups. Other complications, such as need for blood transfusion, platelet transfusion, or fresh frozen plasma (FFP) injection, were not observed. There was no significant difference in terms of complications between the groups. Conclusion: Since blind liver biopsy does not increase the rate of complications, application of this method is recommended for patients without any contraindications, leading to a reduction in the cost of diagnosis and treatment.