In order to evaluate clinical and bacteriological efficacy of Cefpodoxime Proxetil (CP) in typhoid fever in comparison to cefixime (CF), we assessed 140 children with suspected typhoid fever. Fulfilling inclusion criteria finally 40 culture confirmed typhoid fever were allocated in randomized double blind clinical trial (RCT) to receive therapy with either oral CP (16 mg/kg/day, n = 21) or oral CF (20 mg/kg/day, n = 19) for 10 days. The two groups were comparable in their clinical and baseline characteristics. The clinical efficacy was similar in the two groups with only 2 (one in each group) clinical failures and all showing bacteriological eradication on subsequent blood culture. The time of defervescence was comparable in both groups (4.87 Fluconazole Prophylaxis against Fungal Colonization and Invasive Fungal Infection in Very Low Birth Weight Infants 2.33 vs 4.27 +/- 2.28 days, P = 0.308), with no relapse during 3 months follow up and no significant adverse effect. CP reduced the treatment cost by 33% in comparison to cefixime. Our study suggests CP is effective, safe and cheaper oral option for treatment of typhoid fever in children.