In a registry-based cohort study, we determined the risk of invasive illness or death associated with infection with quinolone-resistant Salmonella serotype Typhimurium. We linked data from the Danish surveillance registry of enteric pathogens with data from the Danish civil registration system and 2 national health registries. Of 1323 patients infected with Salmonella Typhimurium, 46 (3.5%) were hospitalized due an invasive illness within 90 days of infection, and 16 (1.2%) died within 90 days of infection. After adjustment for age, sex, and comorbidity, infection with quinolone-resistant Salmonella Typhimurium was associated with a 3.15-fold (95% confidence interval, 1.39-7.10-fold) higher risk of invasive illness or death within 90 days of infection, compared with that observed for infection with pansusceptible strains.