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<p>Abstract</p> <p>Background</p> <p><it>Entamoeba histolytica </it>is an important protozoan intestinal infection in resource-poor settings, including Vietnam. The study objective was to assess risk factors of <it>E. histolytica </it>infection in a community in Vietnam, where wastewater and human excreta are used in agriculture. A case-control study was conducted among residents of Hanam province, Northern Vietnam. Cases (n = 46) infected with <it>E. histolytica </it>and non-infected controls (n = 138) were identified in a cross-sectional survey among 794 randomly selected individuals and matched for age, sex and place of residence. Potential risk factors including exposure to human and animal excreta and household wastewater were assessed with a questionnaire.</p> <p>Results</p> <p>People from households with an average socio-economic status had a much higher risk of <it>E. histolytica </it>infection (odds ratio [OR]=4.3, 95% confidence interval [CI]: 1.3-14.0) compared with those from households with a good socioeconomic status. Those individuals who never or rarely used soap for hand washing had a 3.4 times higher risk for infection (OR=3.4, 95% CI: 1.1-10.0), compared to those who used always soap. In contrast, none of the factors related to use of human or animal excreta was statistically significant associated with <it>E. histolytica </it>infection. People having close contact with domestic animals presented a greater risk of <it>E. histolytica </it>infection (OR = 5.9, 95% CI: 1.8-19.0) than those without animal contact. <it>E. histolytica </it>infection was not associated with direct contact with Nhue river water, pond water and household's sanitary conditions, type of latrine or water source used.</p> <p>Conclusions</p> <p>Our study suggests that in settings where human and animal excreta and Nhue River water are intensively used in agriculture, socio-economic and personal hygiene factors determine infection with <it>E. histolytica</it>, rather than exposure to human and animal excreta in agricultural activities.</p>