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Background: The molecular pathogenesis of severity of illness in typhoid fever is poorly understood. Previous studies have found a direct relationship between flagellar function as determined by motility, and invasiveness in Salmonella species. A previous study revealed that the Hj flagellin genes association of decreased severity of illness, motility and invasiveness of bacteria and compared with Hd flagellin genes. However the role of flagella in in-vivo virulence however remains more controversial. Objectives: In an attempt to elucidate the mechanisms behind severity of typhoid fever in relation with flagellin genes variation, we conducted a prospective and retrospective study to describe the clinical sign & symptoms, flagellin genes variations among from acute and carrier state of typhoid fever patients. Methods: 187 genomic DNA of S. typhi strains from culture of 141 acute typhoid fever and feces of 46 carriers state of typhoid fever who enrolled in several primary health care and hospitals in endemic area of Central Sulawesi, Indonesia. All isolate were examine the Hd, Hj, z66 and z66 Ind of flagellin genes by Polymerase Chain Reaction (PCR). Results: The results of this study revealed that predominant in severity of illness in both acute and carriers state of typhoid fever belong Hd+ and Hd+z66 Ind+ in endemic area of Indonesia. Conclusion: Hd+ and Hd+ z66 Ind+ flagellin gene variation are related to clinical severity of acute typhoid fever.