Typhoid fever is an endemic disease in Iran and other developing countries. This disease has gradually become resistant to the first line of drugs, and because of this resistancy we have studied a new alternative drug (cefixime) on typhoid fever patients and compared it's effectiveness with chloramphenicol. For this purpose, by a randomized clinical trial in Emam Khomeini hospital between 1995-2000, we allocated 44 uncomplicated patient with established typhoid fever (positive blood or bone marrow culture) and by random selection, 24 patient were given cefixime (400 mg PO bid) and 20 patient received chloramphenicol (500 mg po Q6h). The duration of therapy were 10 and 14 days for chloramphenicol and cefixime group respectively. Median fever clearance times were 5±1.9 for cefixime recipients and 3.8±1.2 days for chloramphenicol treated patients, but for improvement in other clinical and laboratory findings, there were not any significant difference. Bacteriologic and clinical cure rate for cefixime was 100 and 92 percents respectively. Though, even cefixime like other betalactam drugs is slow in helping the fever disappearance but our study suggests that oral cefixime is effective and can be used as an alternate treatment of typhoid fever.