Food-borne trematodiases are a group of neglected tropical diseases caused by liver, lung, and intestinal parasitic fluke infections. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2010 study) and a WHO initiative, we assessed the global burden of human food-borne trematodiasis, as expressed in disability-adjusted life years (DALYs) for the year 2005. We systematically searched electronic databases for reports about human food-borne trematodiasis without language restriction, between Jan 1, 1980, and Dec 31, 2008. We used a broad search strategy with a combination of search terms and parasite and disease names. The initial search results were then screened on the basis of title, abstract, and, finally, full text. Relevant quantitative and qualitative data on human prevalence, morbidity, and mortality of food-borne trematodiasis were extracted. On the basis of available information on pathological and clinical appearance, we developed simplified disease models and did meta-analyses on the proportions and odds ratios of specified sequelae and estimated the global burden of human food-borne trematodiasis. We screened 33,921 articles and identified 181 eligible studies containing quantitative information for inclusion in the meta-analyses. About 56·2 million people were infected with food-borne trematodes in 2005: 7·9 million had severe sequelae and 7158 died, most from cholangiocarcinoma and cerebral infection. Taken together, we estimate that the global burden of food-borne trematodiasis was 665,352 DALYs (lower estimate 479,496 DALYs; upper estimate 859,051 DALYs). Furthermore, knowledge gaps in crucial epidemiological disease parameters and methodological features for estimating the global burden of parasitic diseases that are characterised by highly focal spatial occurrence and scarce and patchy information were highlighted. Despite making conservative estimates, we found that food-borne trematodiases are an important cluster of neglected diseases. Swiss National Science Foundation; Institute for Health Metrics and Evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.