BACKGROUND Several studies have shown that orally administered killed cholera vaccines are safe and protective in populations at risk of cholera in developing countries. However, these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children. We have tested an inexpensive, killed whole-cell cholera vaccine developed and produced in Vietnam. METHODS The efficacy of the vaccine was assessed in a large-scale, open field trial in people at least 1 year old residing in 22,653 households in the central coastal city of Hue. Alternate households were assigned vaccine (67,395 people; two doses per person) or no vaccine (67,058 people). Surveillance for cholera was conducted in all Ministry of Health facilities serving this population. Analysis was by intention to treat. RESULTS During an outbreak of El Tor cholera 8-10 months after vaccination, 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group, and 92 cases among age-eligible people allocated to the no-vaccine group (protective impact 60% [95% CI 40-73]). Among the 51,975 people who received the complete two-dose vaccine regimen, the protective efficacy was 66% (46-79): in this subset, the protective efficacy was similar for children aged 1-5 years (68%) and for older people (66%). CONCLUSIONS These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children, who are at highest risk of cholera in endemic settings. An inexpensive, locally produced, and effective oral cholera vaccine may be within reach of the limited health-care budgets of poor countries with endemic cholera, if our findings can be replicated in a randomised double-blind trial.