Between 28 November 2003 and 23 February 2004, 4343 cases and 154 deaths from cholera (case-fatality rate 3·5%) were reported in Lusaka, Zambia. A case-control study was conducted in February 2004 to assess potential transmission routes and prevention strategies. Consumption of raw vegetables was significantly associated with cholera [adjusted odds ratio (aOR) 4·7, 95% confidence interval (CI) 1·7–13, P=0·003). Consumption of a local sardine-like fish was protective (aOR 0·3, 95% CI 0·1–0·7, P=0·008). Hand soap was present in 90% of control homes and 58% of case homes. Observed hand soap was a strongly protective factor (aOR 0·1, 95% CI 0·04–0·4, P=0·001). No water source or treatment practice was significantly associated with cholera. This study documents the importance of foodborne transmission of cholera, illustrates the protective role of hand washing in an epidemic setting, and identifies a novel possible protective factor, a local fish, which warrants further research.