ABSTRACT This retrospective cohort study analyzed data from a Japanese health insurance database to assess the effectiveness of baloxavir ( n = 4822) for preventing severe events compared with oseltamivir ( n = 10,523) in patients with influenza B. The primary endpoint was hospitalization incidence (Days 2–14). The secondary endpoints included intravenous antibacterial drug use, pneumonia hospitalization, heart failure hospitalization, inhalational oxygen requirement, and use of other anti‐influenza drugs. The hospitalization incidence was significantly lower with baloxavir (0.15% vs. 0.37%; risk ratio: 2.48, 95% confidence interval: 1.13–5.43). Pneumonia and additional anti‐influenza therapy were also less frequent with baloxavir, thus supporting its use. Trial Registration: UMIN Clinical Trials Registry Study ID: UMIN000051382