Clonorchiasis is an emerging food-borne trematode infection in Vietnam. Due to the absence of cost-effective preventive measures its control largely relies on morbidity reduction by chemotherapy with praziquantel. We performed a comparative cost estimation of three different diagnostic and intervention approaches in areas of high and low prevalence of clonorchiasis in northern Vietnam in order to select more cost-effective chemotherapy. Our study confirmed that a questionnaire investigating the habit of eating raw, freshwater fish was a rapid, cost-effective and operationally feasible tool for identifying individuals at risk of clonorchiasis in both high-prevalence and low-prevalence areas. The cost of diagnosis and intervention per person and per true positive case was 20-fold higher in low-prevalence areas, regardless of the type of approach. Geographical mapping of high-risk areas prior to screening is, therefore, recommended to maximize the cost-effectiveness of the intervention activities. (C) 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.