Infection with Salmonella enterica serovar Choleraesuis (S. Choleraesuis) in humans can be considered as an endemic disease in certain regions of Taiwan, and the number of cases has increased in recent years. The goal of the case-control study discussed in this article was to identify the possible demographic and environmental risk factors associated with S. Choleraesuis infection in Taiwan. During the period of December 2005 to March 2007, the case-control study was conducted in human patients with Salmonella infection from two medical centers. Structured questionnaires were applied to collect information of relevant risk factors after interviewing 13 culture-confirmed S. Choleraesuis cases and 84 controls with other Salmonella serotype infection. After evaluation by univariate and multivariate statistical models, the results suggested that consumption of groundwater could be an independent risk factor associated with S. Choleraesuis in Taiwan. Therefore, appropriate health education needs to be conducted especially in areas where groundwater is used.