The risk factors for mortality were analysed in a consecutive group of 1158 children presenting to the Aga Khan University Medical Center, Karachi, with multidrug resistant typhoid fever that had been proved on culture. There were 19 deaths, representing an overall case fatality rate of 1.6%. Multidrug resistant typhoid was associated with a more severe clinical illness and higher rates of toxicity, hepatomegaly, hypotensive shock, and death. Irrespective of drug resistance status, typhoid fever was found to be a more severe illness in young infants with significantly higher rates of diarrhoea, hypotensive shock, and mortality. Univariate analysis of admission characteristics associated with increased risk for mortality revealed significant association with younger age (p < 0.05), hypotensive shock or hypothermia (p < 0.001), obtundation (p < 0.001), seizures (p < 0.05), anaemia at admission (p < 0.005), and leucocytosis (p < 0.001). Logistic regression analysis of risk factors for mortality showed persistent association of hypothermia, toxicity, and anaemia with mortality. The data provides evidence that multidrug resistant typhoid in childhood is associated with increased risk of mortality, especially in infancy and closer attention to several risk factors for increased morbidity and case fatality rates may lead to improved outcome of treatment.