Background: Cystic echinococcosis (CE) is a zoonotic infection that occurs worldwide, particularly in endemic areas in the Middle East, including Egypt. Echinococcusgranulosus (E. granulosus) eggs can be accidentally ingested by human in contaminated food or drinks and reach primarily the liver forming hydatid cysts with reported predilection for the right lobe. However, the segmental orientation of hepatic echinococcosis in the light of the clinical presentation and serological findings needs further investigation as such correlation may carry additional clues to guide the therapeutic management and prognostic outcomes. Objective:The present study was designed to determine the relation of anatomical location of intrahepatic hydatid cyst to its development, activity, and host immune response; as well as its potential extrahepatic spread. Material and Methods: A total of 46 patients having liver hydatid cysts were evaluated. Intrahepatic cysts were categorized according to Couinaud's segments by ultrasound examination; and analysis was done regarding cyst size, cyst staging and activity, and extrahepatic spread, in addition to clinical features and patterns of IgG level using two sero-diagnostic tests IHA and ELISA. Results: Hydatid cysts were found in all segments with the exception of segment I. Active cysts were mostly found in segment VII (no. = 11; 47.8%), recording a large diameter size with a mean of 6.55 cm. Inactive cysts recorded statistically significant smaller diameters with a mean of 5.55 cm denoting cyst evolution and degeneration. Serum antibody level correlated significantly with radiological profile of cysts activity in the studied population. Finally, extrahepatic spread was observed in hydatid cysts involving all liver segments with the exception of segment V. Conclusion:Hydatid cysts were found in liver segments II through to VIII. While cysts in segment VII demonstrated large sized active cysts with extrahepatic spread, cysts confined to segment V could pose minimal risk for extrahepatic spread