Background <p>This study aimed to explore the risk factors of serious infections (SI) in patients with large-vessel vasculitis (LVV) in Japan.</p> Methods <p>This observational nested case-control study used an administrative claims database (April 2008 to July 2023) provided by Medical Data Vision Co., Ltd. Patients with Takayasu arteritis (TAK) and giant cell arteritis (GCA) were identified based on age and prescription of oral glucocorticoids (GC) or immunosuppressants following a definite diagnosis code. An SI was defined as an infection-related hospitalization. We identified a maximum of five controls for each case that were matched for sex, age, days of follow-up, and calendar year. The adjusted odds ratios (aORs) and 95% confidence intervals for the association between SI and risk factors were estimated using conditional logistic regression.</p> Results <p>Among 1,856 patients with TAK and 2,149 patients with GCA, 151 (8.1%) and 202 SI cases (9.4%) were identified from the TAK and GCA cohorts, respectively. The respiratory tract was the most frequent site of infection. Injectable GCs were significantly associated with SI. No significant increase in the aORs of tocilizumab was observed in either cohort. Significant comorbid risk factors included diabetes mellitus and malignant tumor in both cohorts; respiratory disease and renal dysfunction in the TAK cohort; and cerebral or cardiovascular disease in the GCA cohort.</p> Conclusion <p>Considering these risk factors, close monitoring, prevention, and management of SI are clinically important to prevent the occurrence of SI in patients with LVV.</p>