OBJECTIVES To evaluate the prognostic impact of anatomic versus nonanatomic resection on the patients' survival after resection of a single hepatocellular carcinoma (HCC). SUMMARY OF BACKGROUND DATA Anatomic resection is a reasonable treatment option for HCC; however, its clinical significance remains to be confirmed. METHODS Curative hepatic resection was performed for a single HCC in 210 patients; the patients were classified into the anatomic resection (n = 156) and nonanatomic resection (n = 54) groups. In 84 patients assigned to the anatomic resection group, segmentectomy or subsegmentectomy was performed. We evaluated the outcome of anatomic resection, including segmentectomy and subsegmentectomy, in comparison with that of nonanatomic resection, by the multivariate analysis taking into consideration 14 other clinical factors. RESULTS Both the 5-year overall survival and disease-free survival rates in the anatomic resection group were significantly better than those in the nonanatomic resection group (66% versus 35%, P = 0.01, and 34% versus 16%, P = 0.006, respectively). In the segmentectomy and subsegmentectomy group, the 5-year overall and disease-free survival rates were 67% and 28%, respectively, both of which were also higher than the corresponding rates in the nonanatomic resection group (P = 0.007 and P = 0.001, respectively). The results of multivariate analysis revealed that anatomic resection was a significantly favorable factor for overall and disease-free survivals: the hazard ratios were 0.57 (95% confidence interval, 0.32-0.99, P= 0.04), and 0.65 (0.43-0.96, P = 0.03). CONCLUSION Anatomic resection for a single HCC yields more favorable results rather than nonanatomic resection.