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Despite being a preventable and treatable disease, cholera remains a public health problem in Sudan. The objective of the outbreak investigation was to identify associated risk factors that would help institute appropriate control measures. A case control study design was chosen to identify the risk factors for cholera in Gadarif State. Multi-variate analysis of identified two risk factors and three preventive factors for cholera in Gadarif City. Risk factors: Buying foods or drinks from street vendors (OR = 71.36), 95 % CI: 16.58–307.14), living in an urban setting (Gadarif City) (OR = 5.38), 95 % CI: 2.10–13.81); and the preventive factors were: Washing hands with water after defecation but without soap (OR = 0.16), 95 % CI: 0.04–0.63) or with soap (OR = 0.01), 95 % CI: 0.00–0.03), washing hands before eating (OR = 0.15), 95 % CI: 0.05–0.51) and taking Oral Cholera Vaccine (OCV) (OR = 0.19, 95 % CI: 0.08–0.44). The effectiveness of OCV (VE) was (Unadjusted VE: 80 %, 95 % CI: 69 %-87 %) or (Adjusted VE = 81.0 %, 95 % CI: 56.0 %-92.0 %). Cholera outbreaks, especially in the setting of a complex humanitarian crises, can spread rapidly, resulting in many deaths, and quickly become a public health crisis. Implementation of a community-wide vaccination campaign using OCV as early as possible during the outbreak while implementing other control measures to target hotspots and at-risk populations would expedite halting outbreaks of cholera and save lives. [ABSTRACT FROM AUTHOR]