An intervention study was carried out in Paediatric wards for a period of one year from January 2003 to December 2003 to determine the efficacy and safety of azithromycin in the treatment of uncomplicated childhood typhoid fever. A total of 50 cases were enrolled in the study. The inclusion criteria of the cases were: documented fever for more than 7 days plus two or more of the following clinical features: toxic appearance, abdominal tenderness, hepatomegaly, splenomegaly, diarrhoea, constipation and coated tongue plus positive Widal test and/or blood culture positivity. Patients who had complication like gastrointestinal tract (GIT) haemorrhage; intestinal perforation and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg /day for a period of 07 days. The time to defervescence was 3.82+/-1.49 days. The minimum defervescence time was 02 days and maximum was 07 days. Clinical cure rate was 94%. No serious adverse effect was noted related to azithromycin therapy except nausea, vomiting, and jaundice. Prior treatment with antibiotics did not affect defervescence time (P>0.05). Pre-treatment febrile period has got positive and linear correlation with clinical response (r = +0.593). It was found that once daily administration of oral azithromycin for seven days in the treatment of uncomplicated typhoid fever was effective and reasonably safe.