The pathogenicity of norovirus is definitively established. However, norovirus is frequently detected in the stool of healthy individuals. To gain understanding of the apparent high prevalence of asymptomatic infection, we analyzed a dynamic transmission model of norovirus infection, disease, and immunity. We simulated norovirus epidemiology in low- and high-transmission settings by varying the basic reproduction number (R0). We predicted annual disease incidence values in children aged 0-4 years of 25% with a low R0 and 29% with a high R0. However, the point prevalence of asymptomatic infection rose sharply from 3% to 48% from the low to high R0 settings. Among older children and adults, the models projected that incidence of disease would rise from 6% to 16% from the low to high R0 settings, whereas asymptomatic infection prevalence was lower in this age group. Asymptomatic prevalence of norovirus can change dramatically with small changes in R0. The ratio of prevalence in cases to controls could be high in a developed country and close to or even less than 1 in a high-exposure setting, despite similar disease incidence. These findings highlight an important limitation of case-control studies for pathogens for which there is suboptimal diagnostic specificity.