Background. Listeriosis is a leading cause of death among patients with foodborne diseases in the United States. Monitoring disease incidence is an important element of listeriosis surveillance and control. Method. We conducted population-based surveillance for Listeria monocytogenes isolates obtained from normally sterile sites at all clinical diagnostic laboratories in the Foodborne Diseases Active Surveillance Network from 1996 through 2003. Results. The incidence of laboratory-confirmed invasive listeriosis decreased by 24% from 1996 through 2003; pregnancy-associated disease decreased by 37%, compared with a decrease of 23% for patients ≥50 years old. The highest incidence was reported among Hispanic persons from 1997 through 2001. Differences in incidence by age group and ethnicity may be explained by dietary preferences. Conclusion. The marked decrease in the incidence of listeriosis may be related to the decrease in the prevalence of L. monocytogenes contamination of ready-to-eat foods since 1996. The crude incidence in 2003 of 3.1 cases per 1 million population approaches the government's Healthy People objective of 2.5 cases per 1 million population by 2005. Further decreases in listeriosis incidence will require continued efforts of industry and government to reduce contamination of food and continued efforts to educate consumers and clinicians.