BACKGROUND: Infections with nontyphoidal Salmonella cause an estimated 19,336 hospitalizations each year in the United States. Sources of infection can vary by state and include animal and plant-based foods, as well as environmental reservoirs. Several studies have recognized the importance of increased ambient temperature and precipitation in the spread and persistence of Salmonella in soil and food. However, the impact of extreme weather events on Salmonella infection rates among the most prevalent serovars, has not been fully evaluated across distinct U.S. regions. METHODS: To address this knowledge gap, we obtained Salmonella case data for S. Enteriditis, S. Typhimurium, S. Newport, and S. Javiana (2004-2014; n = 32,951) from the Foodborne Diseases Active Surveillance Network (FoodNet), and weather data from the National Climatic Data Center (1960-2014). Extreme heat and precipitation events for the study period (2004-2014) were identified using location and calendar day specific 95(th) percentile thresholds derived using a 30-year baseline (1960-1989). Negative binomial generalized estimating equations were used to evaluate the association between exposure to extreme events and salmonellosis rates. RESULTS: We observed that extreme heat exposure was associated with increased rates of infection with S. Newport in Maryland (Incidence Rate Ratio (IRR): 1.07, 95% Confidence Interval (CI): 1.01, 1.14), and Tennessee (IRR: 1.06, 95% CI: 1.04, 1.09), both FoodNet sites with high densities of animal feeding operations (e.g., broiler chickens and cattle). Extreme precipitation events were also associated with increased rates of S. Javiana infections, by 22% in Connecticut (IRR: 1.22, 95% CI: 1.10, 1.35) and by 5% in Georgia (IRR: 1.05, 95% CI: 1.01, 1.08), respectively. In addition, there was an 11% (IRR: 1.11, 95% CI: 1.04-1.18) increased rate of S. Newport infections in Maryland associated with extreme precipitation events. CONCLUSIONS: Overall, our study suggests a stronger association between extreme precipitation events, compared to extreme heat, and salmonellosis across multiple U.S. regions. In addition, the rates of infection with Salmonella serovars that persist in environmental or plant-based reservoirs, such as S. Javiana and S. Newport, appear to be of particular significance regarding increased heat and rainfall events.