This is an interventional prospective pre-post clinical study aimed to evaluate the clinical management of the short course treatment of oral Cefixime in Egyptian hospitalized children with typhoid fever. A final population of 30 children with proven Widal test and blood culture typhoid fever was conducted in the clinical study. All cases received oral Cefixime at admission with a dosage regimen 20 mg/kg/day in divided doses for 7 days. The 30 analyzed cases consumed 3.9 ± 1.4 (Mean ± SD) day as a time for fever defervescence. All isolates were sensitive to Cefixime while the highest resistance was observed with Cotrimoxazole (63.33%) followed by Ampicillin (53.33%) and Chloramphenicol (43%). The clinical cure and bacteriological eradication were observed in 90% of the children while one case (3.3%) relapsed within one month so 86.7% cure rate was documented by this study. No severe side effects were detected during treatment; only 2 (6.7%) cases had diarrhea and one (3.3%) case got skin rash without requiring discontinuation of therapy. No mortality reported. Cefixime was well tolerated by most of the children. This study proposed short course treatment of Cefixime as safe and efficient oral option for the management of typhoid fever in children.