We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household-and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0.89, 95% confidence interval (CI) 0.83-0.95], was higher with an increase in population density (RR 1.13, 95% CI 1.05-1.21) and was lower in the households using a safe drinking-water source (RR 0.63, 95% CI 0.41-0.99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.