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In this study, a real-time compression based ultrasound elasticity imaging prototype was developed and evaluated for liver radio-frequency ablation (RFA) assessment under ex vivo and in vivo conditions. The prototype was implemented on a commercial ultrasound system (iU22, Philips Healthcare) for an L12-5 linear transducer and a C5-1 curvilinear transducer. Under the ex vivo condition, two bovine liver samples were used for L12-5 and C5-1 respectively. Under the in vivo condition, a pig was anesthetized and mechanically ventilated. Ultrasound elasticity imaging experiments were performed during breath-hold in order to reduce respiratory motion artifacts. Post-RFA strain images were compared against several imaging modalities including MRI, contrast-enhanced CT and gross pathology. For the ex vivo case, a Rita Starburst probe (AngioDynamics, Queensbury, NY) was used to perform RFA and induce tissue deformation for strain imaging. Real-time strain images were generated pre- and post-RFA. After the ablation, the liver was imaged by a Panorama 1-T MRI system (Philips Healthcare), then it was dissected along the approximate ultrasound imaging plane for lesion dimension measurement using a caliper. The post-RFA strain images depicted an ablation zone with increased stiffness that was well correlated with the physiological changes observed in the T1-weighted MR image and gross pathology. For the second ex vivo liver sample, the strain image revealed an ablation zone of 4.90 cm ? 2.85 cm, and the MR image and gross pathology showed a zone of 4.56 cm ? 3.24 cm and of 4.91 cm ? 3.65 cm, respectively. For the in vivo study, three different commercial RFA needles were employed: the Covidien (Mansfield, MA) CoolTip single prong and triple-cluster probes, and the Rita Starburst probe. The animal underwent contrast-enhanced CT imaging immediately after RFA. It was then sacrificed and the ablated liver lobes were dissected for ex vivo MRI. All three imaging modalities showed compar- able measurement of lesion dimensions. The triple-cluster Covidien probe and the Rita probe with expanding tines seemed to perform better with elasticity assessment than the Covidien single prong probe. Preliminary results from this study demonstrate that real-time ultrasound strain imaging is potentially a valuable tool for assessing liver RFA. Further technical development of this prototype will advance toward real-time clinical use.