272 Background: Percutaneous ablation and transarterial chemo- or radioembolization are commonly used in the treatment of HCC and mCRC to the liver. IRE using the Nanoknif is more versatile than other ablative modalities (such as RFA) in that tumors abutting vascular structures can be treated with IRE without compromise of the vessels or concern for the heat sink effect of nearby blood flow. Methods: We examined the records of patients (pts) referred for IRE for HCC and mCRC. The procedures were all done percutaneously under general anesthesia using a standard protocol. The primary endpoint was progression-free survival (PFS). Responses were assessed using the modified RECIST criteria. Results: Between 1/2010 and 8/2011, 49 pts underwent percutaneous ablation of unresectable HCC and mCRC liver tumors using IRE – 33 with HCC and 16 with mCRC. A total of 76 lesions were treated in 62 sessions; the median number of lesions treated per patient was 1 (range 1-4) and the median tumor size treated was 2.1cm (range 0.8-6). After IRE, 20 pts (41%) had a complete response (CR), 19 (39%) had a partial response and 10 (20%) had stable disease as their best response. The Kaplan-Meier estimated median PFS was 11.3 months (95% CI 9.6-12.9) for all pts, 11.6 months (95% CI 10.2-12.9) for HCC pts, and 10.4 months (95% CI 5.4-15.4) for mCRC patients. The one-year PFS was significantly higher for pts achieving a CR compared to those who did not achieve a CR (75% versus 59%, log rank p = 0.05). The number of liver lesions at baseline and size of the treated lesions were not associated with any differences in survival. The IRE was complicated in 6 pts (12%) by pneumothorax (2), pleural effusion (2), and atrial flutter/fibrillation during anesthesia (2). All pts recovered fully from these complications. One pt died within 1 month of the IRE due to disease progression. Conclusions: IRE of liver tumors is safe. The PFS rates for pretreated mCRC and unresectable HCC are promising. A complete lack of enhancement of the treated lesion on the post-IRE CT scan appears to be associated with longer survival.