© 2015, Springer Science+Business Media New York. Aim: The aim of this study is to compare tumoral microvessel density (MVD) and overall survival in two different groups of hepatocellular carcinoma (HCC), namely, viral hepatitis-related HCC (VHr-HCC) versus non-hepatitis-related HCC (NHr-HCC). Methods: Seventy-eight consecutive cases of HCC (47 hepatitis and 31 non-hepatitis cases) were studied. Microvessel numbers were assessed by staining for the antigens CD31, CD34, and CD240. The highest number of microvessel density and number of vessels were counted in the tumor, and the mean value represented the final MVD. Overall survival (OS) was analyzed between the two groups. Results: VHr-HCC and NHr-HCC were observed in 47 and 31 cases, respectively. No significant differences were seen between the VHr-HCC and NHr-HCC groups with respect to age, gender, or Child-Pugh class distribution. Mean number of vessels was significantly higher in Hr-HCC using CD31 (97.7 vs 83.7) and CD34 (82.4 vs 71.9) (p value 0.025 and 0.039, respectively). Higher MVD was detected in Hr-HCC compared to NHr-HCC using CD31 (4.9 vs 4.4) and CD34 (4.7 vs 4.3) (p value 0.0095 and 0.0190, respectively). No significant difference was observed between VHr-HCC and NHr-HCC using CD240 immunostaining for MVD (p value 0.0945 and 0.906, respectively). Overall survival was not statistically significantly different between VHr-HCC and NHr-HCC groups (p value 0.104). Conclusions: HCC due to viral hepatitis has higher tumor microvessel formation and higher MVD values. This observation may explain the higher response of agents that target vascular endothelial growth factor (such as sorafenib) in patients with VHr-HCC.