Quantitative estimates of the relative risk (RR) of listeriosis among higher-risk populations and a nuanced understanding of the age-specific risks are crucial for risk assessments, targeted interventions, and policy decisions. The RR of invasive listeriosis was evaluated by age, pregnancy status, and ethnicity using 2004-2009 data from the Foodborne Diseases Active Surveillance Network (FoodNet). Nonparametric logistic regression was used to characterize changes in risk with age and ethnicity. Adjusted RRs and 95% confidence intervals (CIs) were evaluated using negative binomial generalized linear models. Among non-pregnancy-associated cases, listeriosis incidence rates increased gradually with age (45-59 years: RR, 4.7; 95% CI, 3.3-6.8; >85 years: RR, 53.8; 95% CI, 37.3-78.9; reference: 15-44 years). The RR was significantly higher for Hispanics than for non-Hispanics (RR, 1.8; 95% CI, 1.3-2.5). Among women of reproductive age (15-44 years), pregnant women had a markedly higher listeriosis risk (RR, 114.6; 95% CI, 68.9-205.1) than nonpregnant women. The RR was higher for Hispanic than non-Hispanic women, regardless of pregnancy status, and this increased during the study period (2004-2006: RR, 1.9; 95% CI, 1.0-3.3; 2007-2009: RR, 4.8; 95% CI, 3.1-7.1). This study quantifies the increases in risk of listeriosis among older persons, pregnant women, and Hispanics in the United States. Additional research is needed to better describe the independent effects of age on risk while accounting for underlying conditions. These estimates are needed both to optimize risk assessment models and to inform targeted interventions and policy decisions.