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The efficacy of a Salmonella vaccine for reducing fecal shedding of Salmonella during the finishing period and lymph node (LN) carriage at harvest was investigated in commercial feedlot cattle. The study was designed as a pen-level randomized complete block with two treatment groups, a Salmonella Newport siderophore receptor and porin proteins-based vaccine (VAC) and a nonvaccinated control (CON). Cattle were randomly allocated into 24 pens within 12 blocks based on the time of allocation. Twenty to 25 fecal pats were collected from each of the study pen floors once a month from June to August 2013. During harvest, a minimum of 25 sub-iliac LN were collected from carcasses within each study pen. Fecal and pulverized LN samples were cultured for Salmonella quantification and detection. Mixed models were used to analyze the effect of vaccination on fecal shedding and LN carriage of Salmonella. Montevideo and Anatum were the predominant Salmonella serotypes among fecal samples and LNs; no Newport isolates were recovered. Vaccination was not significantly associated (p = 0.57) with the prevalence of Salmonella in feces over time; the mean within-pen prevalence was 62.3% and 66.0% among VAC and CON, respectively. Sampling month was significantly associated (p