BACKGROUND: Azithromycin is the only oral option available for XDR enteric fever. Studies correlating azithromycin levels with treatment success are rare. METHODS: Serum azithromycin levels after administration of a once-daily 20 mg/kg dose for 7 days were measured in a single-centre prospective cohort of 25 consecutive adults with blood culture-positive enteric fever. Five blood samples were collected on Day 2 after starting azithromycin, i.e. 30 min before dosing (trough), and 2, 5, 12 and 24 h after dosing. The MIC was determined for all isolates and azithromycin plasma concentration was determined using LC-MS. Clinical and microbiological outcomes were documented. CONCLUSIONS: Azithromycin was effective in treatment of enteric fever, despite low extracellular azithromycin plasma levels.