Although salmonellosis is a common endemo-epidemic disease in Benin, there is a paucity of data about it. The purpose of this cross-sectional study was to determine the incidence of major salmonellosis requiring hospitalizaton and to describe its epidemiological, clinical, and serologic features as well as treatment and outcome. Consecutive cases observed at the Medical Department of Parakou University Hospital in Benin between January 1, 2005 and December 31 2007 were included. Salmonellosis was defined on the basis of clinical and serological criteria. Among the 2,520 patients hospitalized during the study period, salmonellosis was diagnosed in 135 (5.4% [95% CI 4.5%-6.3%]). Highest incidences were observed in January, July, October and November. The main symptoms were headache, fever, fatigue and abdominal pain. The Salmonella typhi serotype was identified in 94.8% of patients. Two patients presented co-infection, i.e., Salmonella typhi with paratyphi A in one case and Salmonella typhi with paratyphi B in the other. Fluoroquinolones were used for treatment in 79.3% of patients. Outcome was favorable in 62.2%. The main complications were,typhoid digestive perforation in 11.1%, and gastrointestinal bleeding in 8.1%. The mortality rate was 4.4% (n=6). These data are consistent with previous reports in the literature and confirm the frequency and severity of salmonellosis in Benin.