Background: Dengue is a prevalent cause of acute febrile illness, predominantly in Asia, where it necessitates supportive care without the need for antibiotics. This study aimed to evaluate antibiotic usage and analyze hospitalization costs among adults infected with the dengue virus., Methods: This retrospective cohort study was conducted at the Hospital for Tropical Diseases, Thailand, in 2022. Two independent reviewers assessed all adult cases with confirmed dengue from 2016 to 2021. Determinants of inappropriateness were analyzed using Poisson regression., Results: The study included 249 participants with over half presenting with severe dengue or dengue with warning signs upon admission. The cumulative incidence of antibiotic use was 9.3% (95% CI, 8.23-10.47), predominantly involving empirical treatment strategies. Ceftriaxone and doxycycline were the most frequently prescribed antibiotics. Notably, patients who received empirical antibiotics showed no definite or presumed bacterial infections. Among those who received definite strategies, inappropriate durations, including both short treatments and the overuse of broad-spectrum antibiotics, were observed. A private ward admission was identified as a significant predictor of inappropriate use, with an incidence rate ratio of 4.15 (95% CI, 1.16-14.82) compared with intensive care unit admission. Direct medical costs did not differ significantly between appropriate and inappropriate uses., Conclusions: The incidence of antibiotic use among dengue cases was moderate; however, inappropriate use by indication was observed. Antimicrobial stewardship strategies should be encouraged, particularly in patients with dengue with warning signs admitted to a general or private ward. Direct medical costs between appropriate and inappropriate use were comparable., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)