During the Escherichia coli O157:H7 outbreak in 2006 in the United States, the primary strategy to prevent illness was to advise consumers not to eat spinach. No widespread warnings were issued about preventing person-to-person (secondary) transmission. A disease transmission model, fitted to the current data, was used to investigate likely reductions in illnesses that could result from interventions to prevent secondary transmission. The model indicates that exposure to contaminated spinach occurred early in the outbreak and that secondary transmission was similar to that in previous E. coli outbreaks ( 12%). The model also suggests that even a modestly effective strategy to interrupt secondary transmission (prevention of only 2%-3% of secondary illnesses) could result in a reduction of 5%-11% of symptomatic cases. This analysis supports the use of widespread public health messages during outbreaks of E. coli O157:H7 with specific advice on how to interrupt secondary transmission.