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Background: We have been utilizing both resection and laparoscopic radiofrequency ablation (RFA) to treat hepatocellular carcinoma (HCC). The aim of this study is to describe patient characteristics and outcome for each treatment modality from a single institution. Methods: Medical records of HCC patients who underwent resection ( n = 92) or laparoscopic (RFA) ( n = 92) between 1997 and 2010 were reviewed. Univariate Kaplan-Meier and multivariate Cox proportional-hazards model were used to analyze survival. Results: Patients with normal liver function and larger tumors were resected, and those with liver dysfunction, portal hypertension, and multiple tumors were ablated. Tumor size was larger in the Resection group, whereas number of tumors was higher in the RFA group. Child class and Barcelona Clinic Liver Cancer (BCLC) staging were more advanced in the RFA group. Hospital stay was longer, and morbidity and mortality higher in the Resection versus the RFA group. There was no difference in disease-free survival, but the 5-year actual survival was significantly higher (40% versus 21%) in the Resection group. On univariate analysis, number of tumors, tumor size, platelet count, BCLC stage, Child class, and type of surgery were predictors of overall survival. On multivariate analysis, Child class and number of tumors were independent predictors of overall survival. Conclusions: To our knowledge, this is the largest North American series reporting on RFA and resection for HCC from a single institution. Herein, we describe the perioperative and oncologic outcomes to be expected when these modalities are used in a certain treatment algorithm. [ABSTRACT FROM AUTHOR]