SummaryBackgroundDomesticated animal ownership is an understudied aspect of the human environment that influences mosquito biting behaviour and malaria transmission, and is a key part of national economies and livelihoods in malaria-endemic regions. In this study, we aimed to understand differences inPlasmodium falciparumprevalence by ownership status of common domesticated animals in DR Congo, where 12% of the world's malaria cases occur and anthropophilicAnopheles gambiaevectors predominate.MethodsIn this cross-sectional study, we used survey data from individuals aged 15–59 years in the most recent (2013–14) DR Congo Demographic and Health Survey and previously performedPlasmodiumquantitative real-time PCR (qPCR) to estimateP falciparumprevalence differences by household ownership of cattle; chickens; donkeys, horses, or mules; ducks; goats; sheep; and pigs. We used directed acyclic graphs to consider confounding by age, gender, wealth, modern housing, treated bednet use, agricultural land ownership, province, and rural location.FindingsOf 17 701 participants who had qPCR results and covariate data, 8917 (50·4%) of whom owned a domesticated animal, we observed large differences in malaria prevalence across types of animals owned in both crude and adjusted models. Household chicken ownership was associated with 3·9 (95% CI 0·6 to 7·1) moreP falciparuminfections per 100 people, whereas cattle ownership was associated with 9·6 (–15·8 to –3·5) fewerP falciparuminfections per 100 people, even after accounting for bednet use, wealth, and housing structure.InterpretationOur finding of a protective association conferred by cattle ownership suggests that zooprophylaxis interventions might have a role in DR Congo, possibly by drawingAn gambiaefeeding away from humans. Studies of animal husbandry practices and associated mosquito behaviours could reveal opportunities for new malaria interventions.FundingThe National Institutes of Health and the Bill & Melinda Gates Foundation.TranslationsFor the French and Lingala translations of the abstract see Supplementary Materials section.