Objective: To evaluate the applicability, reproducibility, and diagnostic performance of a new 2D-shear wave elastography (SWE) using the comb-push technique (2D CP-SWE) for detection of hepatic fibrosis, using histopathology as the reference standard. Materials and methods: This prospective study was approved by the institutional review board, and informed consent was obtained from all patients. The liver stiffness (LS) measurements were obtained from 140 patients, using the new 2D-SWE, which uses comb-push excitation to produce shear waves and a time-aligned sequential tracking method to detect shear wave signals. The applicability rate of 2D CP-SWE was estimated, and factors associated with its applicability were identified. Intraobserver reproducibility was evaluated in the 105 patients with histopathologic diagnosis, and interobserver reproducibility was assessed in 20 patients. Diagnostic performance of the 2D CP-SWE for hepatic fibrosis was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The applicability rate of 2D CP-SWE was 90.8% (109 of 120). There was a significant difference in age, presence or absence of ascites, and the distance from the transducer to the Glisson capsule between the patients with applicable LS measurements and patients with unreliable measurement or technical failure. The intraclass correlation of interobserver agreement was 0.87, and the value for the intraobserver agreement was 0.95. The area under the ROC curve of LS values for stage F2 fibrosis or greater, stage F3 or greater, and stage F4 fibrosis was 0.874 (95% confidence interval [CI]: 0.794-0.930), 0.905 (95% CI: 0.832-0.954), and 0.894 (95% CI: 0.819-0.946), respectively. Conclusion: 2D CP-SWE can be employed as a reliable method for assessing hepatic fibrosis with a reasonably good diagnostic performance, and its applicability might be influenced by age, ascites, and the distance between the transducer and Glisson capsule.