A multi-state outbreak of Salmonella enterica serovar Saintpaul infection occurred in Australia during October 2006. A case-control study conducted in three affected jurisdictions, New South Wales, Victoria and Australian Capital Territory, included 36 cases with the outbreak-specific strain of S. Saintpaul identified by multiple locus variable-number tandem repeat analysis (MLVA) in a faecal specimen and 106 controls. Consumption of cantaloupe (rockmelon) was strongly associated with illness (adjusted OR 23·9 95%, 95% CI 5·1–112·4). S. Saintpaul, with the outbreak MLVA profile, was detected on the skin of two cantaloupes obtained from an implicated retailer. Trace-back investigations did not identify the specific source of the outbreak strain of S. Saintpaul, but multiple Salmonella spp. were detected in environmental samples from farms and packing plants investigated during the trace-back operation. Cantaloupe production and processing practices pose a potential public health threat requiring regulatory and community educational interventions.