Background: In April 2015, the Missouri Department of Health and Senior Services identified a cluster of four Salmonella enterica serovar Oranienburg infections among residents of the St. Louis metro area. Clinical isolates from those patients shared an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern. Methods and Findings:The ensuing outbreak investigation included epidemiological, laboratory, and environmental investigations. Clinical and environmental isolates were subtyped by PFGE pattern and whole genome sequencing (WGS). Eggs from a single poultry farm and processing facility were identified as the likely source of this outbreak based on the epidemiologic data, highly related Salmonella isolates from the farm and processing facility, and clinical isolates from patients. The egg farm operations were suspended, and the producer issued a voluntary recall of all eggs produced up to the time of the recall.Conclusions: WGS is a valuable tool for Salmonella Oranienburg infection outbreak investigation. Early prospective application of WGS enhances several aspects of the outbreak investigation. A thorough analysis of combined epidemiological, traceback, and advanced molecular laboratory data is needed for the proper management of foodborne outbreak investigation.

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