This field study investigated the efficacy of a Salmonella Choleraesuis live vaccine (Argus SC) to reduce the number of infections with Salmonella. Twelve groups of about 380 pigs each were randomly allocated to either vaccination (V) or no vaccination (C). The vaccine was applied orally at 3 and 16 weeks. Forty pigs per group were blood sampled at 3, 10, 16, and 24 weeks to detect possible antibodies against Salmonella. The prevalence of Salmonella in the lymph nodes was the major variable. In the V groups, only 0.6% of the lymph nodes were positive, whereas 7.2% were positive in the C groups (p < 0.001). The percentage of seropositive pigs at 24 weeks (cut-off OD > 10) was 26% and 9% in the V and C groups, respectively (p < 0.001). The present study documented that vaccination with a live modified S. Choleraesuis vaccine is a useful tool to lower the prevalence of Salmonella in swine herds.