Background. Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. Clarifying the viral, host, and environmental factors (epidemiologic triad) associated with severe outcomes can help target public health interventions. Methods. Acute norovirus outbreaks reported to the National Outbreak Reporting System (NORS) in 2009?2016 were linked to laboratory-confirmed norovirus outbreaks reported to CaliciNet. Outbreaks were analyzed for differences in genotype (GII.4 vs non-GII.4), hospitalization, and mortality rates by timing, setting, transmission mode, demographics, clinical symptoms, and health outcomes. Results. A total of 3747 norovirus outbreaks were matched from NORS and CaliciNet. Multivariable models showed that GII.4 outbreaks (n = 2353) were associated with healthcare settings (odds ratio [OR], 3.94 [95% confidence interval {CI}, 2.99?5.23]), winter months (November?April
1.55 [95% CI, 1.24?1.93]), and older age of cases (?50% aged ?75 years
1.37 [95% CI, 1.04?1.79]). Severe outcomes were more likely among GII.4 outbreaks (hospitalization rate ratio [RR], 1.54 [95% CI, 1.23?1.96]
mortality RR, 2.77 [95% CI, 1.04?5.78]). Outbreaks in healthcare settings were also associated with higher hospitalization (RR, 3.22 [95% CI, 2.34?4.44]) and mortality rates (RR, 5.65 [95% CI, 1.92?18.70]). Conclusions. Severe outcomes more frequently occurred in norovirus outbreaks caused by GII.4 and those in healthcare settings. In conclusion, these results should help guide preventive interventions for targeted populations, including vaccine development.