BACKGROUND: Listeriosis caused by Listeria monocytogenes has a high case-fatality rate (CFR) of approximately 20% to 30%. An increasing incidence of listeriosis has been reported in many countries recently. We investigated the annual incidence, clinical characteristics, and outcomes of listeriosis at three different hospitals in Korea and evaluated the effects of appropriate empiric antimicrobial treatments on patient outcomes. METHODS: We retrospectively collected the data of all culture-positive cases of human listeriosis from three hospitals of different sizes in Korea during 2006-2016 and calculated the annual number of cases and incidence per 100,000 admissions. RESULTS: A total of 58 patients with L. monocytogenes were included in this study. The incidence of listeriosis was significantly higher in 2013-2016 than in 2006-2012 (RR 3.1; 95% CI 1.79-5.36; P<0.001), mainly because of an increase in patients over 60 years of age (RR 3.69; 95% CI 1.70-8.02; P<0.001). Multivariate analysis showed that healthcare-associated infection (adjusted OR, 12.15; 95% CI, 2.56-86.01; P=0.004) and empirical treatment with first-line antimicrobial agents (adjusted OR, 0.08; 95% CI, 0.00-0.63; P=0.044) were associated with CFR. CONCLUSIONS: Healthcare-associated infections caused by L. monocytogenes are associated with high CFR. Adequate initial empirical treatments could reduce CFR, suggesting that careful consideration of an empirical antimicrobial regimen is warranted for elderly or immunocompromised patients admitted to the hospital.