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Background Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital’s catchment area, Gedaref State, Sudan. Methods From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire. Results Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard’s immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants. Discussion and conclusion Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures., Author Summary Visceral leishmaniasis (VL), a fatal disease without treatment, is caused by a parasite (Leishmania) transmitted to humans through sandflies. Its epidemiology and the vectors involved in its transmission differ importantly between endemic zones. Preventive measures aim at reducing the parasite reservoirs and at limiting human exposure to sandflies. In Sudan, there is a lack of knowledge on VL risk and protective factors, limiting the possibility of development of control strategies. We conducted a study in a VL endemic area, Gedaref State (Sudan), to identify individual and household level determinants of clinical VL. We compared several characteristics of VL patients and inhabitants free of VL. We found that having a household member sick with VL in the previous year was the strongest VL risk factor. VL risk also seemed to be influenced by the household size, sleep location, evening outdoor activities, use of some repellents, and proximity to dogs at night. VL risk also appeared to decrease with a buffer distance between adjacent house yard and with the proximity to animals other than dogs at night. Our findings provide useful suggestions for guiding further intervention studies on VL preventive measures.