Purpose: To describe an in vitro blood-perfused bovine liver model for the testing of radiofrequency (RF) ablation devices and compare the performance of a specific RF ablation device in the model relative to three other biologic models. Materials and Methods: Fresh bovine livers were used to create three in vitro models: blood-perfused, KrebsHenseleit (KH) solutionperfused, and nonperfused. The perfused models were connected to a heartlung machine via the portal vein and perfused with heparinized autologous blood or KH solution under physiologic conditions. Six swine were used as in vivo liver models. A cluster electrode and RF ablation system was operated in impedance mode for 12 minutes in all models. Ablated livers were sectioned, with long- and short-axis measurements of the ablations obtained, and statistical analysis was performed. Results: A total of 39, 23, 17, and 12 ablations were performed in 14, 6, 5, and 6 blood-perfused bovine livers, KH solutionperfused bovine livers, nonperfused bovine livers, and in vivo porcine livers, respectively. On cut specimens, the average diameters of ablation zones were 4.00 cm (95% CI, 3.88-4.13) in blood-perfused livers, 4.34 cm (95% CI, 4.14-4.50) in KH solutionperfused livers, 4.67 cm (95% CI, 4.50-4.83) in nonperfused livers, and 3.56 cm (95% CI, 3.26-3.83) in in vivo porcine livers. In all models, the ablation zone diameters were normally distributed. Conclusions: In the in vitro blood-perfused bovine liver model, the size of ablations produced by an RF ablation device are closer in size to those seen in porcine liver in vivo compared with the lesions produced in KH solutionperfused or nonperfused bovine liver. © 2011 SIR.