Background: While typhoid fever is common in our environment, presentation with jaundice is unusual. The aim of this study has been to determine the clinical and laboratory features that allow early diagnosis of typhoid fever in patients that present with jaundice and differentiate it from other common causes of fever and jaundice in the tropics.Materials and Methods: This prospective study was conducted between May 1997 and October 1998 at Center Hopitalier Regional de Hombo Anjuoan, Comoros Islands. Patients with clinical and laboratory evidence of typhoidfever were included. Viral or toxic hepatitis, chronic liver disease, sickle cell disease and other causes of jaundice were excluded by clinical examination and appropriate investigations. Serial evaluation of liver function test and abdominal ultrasound were done. Patients were resuscitated with fluids and electrolytes and treated with appropriateantibiotics. Liver involvement was determined using clinical and laboratory parameters.Results: Of the 254 patients with confirmed diagnosis of typhoid fever, 31 (12.2%) presented with jaundice. Their mean age was 24.6 ± 9.2SD years. Fever preceded the appearance of jaundice by 8-27 days. In 27 (87.1%) patients, there was hepatosplenomegaly. Serum bilirubin ranged 38 – 165 umol/l with mean of 117 ± 14SD. Conjugated bilirubin ranged 31-150 umol/l with mean of 95 ± 8SD. Serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were raised with mean values of 180, 105 and 136 IU, respectively. Six (19.4%) patients died compared to 12.1% of non-icteric patients.Conclusion: Typhoid patients may present with varying degrees of jaundice and fever that may be confused with viral, malarial or amebic hepatitis, diseases that are common in the tropics. Physical examination and simple biochemical tests would identify the typhoid patients who should be treated with appropriate antibiotics even before the results of blood culture are available.