OBJECTIVES: Little is known about the economic burden of influenza-related hospitalizations in Japan. This study sought to identify the factors that contribute to the total healthcare costs (THCs) associated with hospitalizations due to influenza in the Japanese population. STUDY DESIGN: A retrospective cross-sectional database analysis study. METHODS: A structural equation modelling approach was used to analyse a nationwide Japanese hospital claims data. This study included inpatients with at least 1 confirmed diagnosis of influenza and with a hospital stay of at least 2 days, who were admitted between April 2014 and March 2015. RESULTS: A total of 5261 Japanese inpatients with a diagnosis of influenza were included in the final analysis. The elderly (>/=65 years) and the young (=15 years) comprised more than 85% of patients. The average length of stay (LOS) was 12.5 days, and the mean THC was 5402 US dollars (US$) per hospitalization. One additional hospital day increased the THC by 314 US$. Intensive care unit hospitalizations were linked to higher costs (+4957 US$) compared to regular hospitalizations. The biggest procedure-related cost drivers, which were also impacted by LOS, were blood transfusions (+6477 US$), tube feedings (+3501 US$) and dialysis (+2992 US$). CONCLUSIONS: In Japan, the economic burden due to influenza-related hospitalizations for both children and the elderly is considerable and is further impacted by associated comorbidities, diagnostic tests and procedures that prolong the LOS.