Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.