Objective: To examine the epidemiology, time trends, and outcomes and types of serious infections in people with vasculitis in the US. Methods: We identified people with vasculitis who were hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections, or opportunistic infections in the 1998–2016 US National Inpatient Sample. We used adjusted logistic regression to examine the predictors of a hospital stay >3 days, total hospital charges greater than the median, discharge to a non-home setting, and in-hospital mortality. Results: We noted 111,345 serious infections in patients with vasculitis (14% of all vasculitis hospitalizations). Among the patients, the mean age was 67.3 years, the Deyo-Charlson comorbidity index score was ≥2 in 54%, 37% were male, and 67% were White. The serious infection hospitalization rate per 100,000 US National Inpatient Sample claims in 1998–2000 versus 2015–2016 (and rates of increase) in patients with vasculitis was as follows: overall, 12.14 versus 25.15 (2.1-fold); opportunistic infections, 0.78 versus 0.83 (1.1-fold); skin and soft tissue infections, 1.38 versus 2.52 (1.8-fold); UTI, 0.35 versus 1.48 (4.2-fold); pneumonia, 7.10 versus 6.23 (0.9-fold); and sepsis, 2.53 versus 14.10 (5.6-fold). Pneumonia was the most common serious infection in 1998–2000 (58%) versus sepsis in 2015–2016 (56%). Sepsis, older age, Deyo-Charlson comorbidity index score of ≥2, urban hospital, or medium/large hospital (by number of beds) were associated with higher health care utilization and in-hospital mortality rates; Northeast region and Medicare and Medicaid payer type were associated with higher rates of health care utilization. Conclusion: Serious infection hospitalization rates are increasing in patients with vasculitis except among those with pneumonia. Sepsis was the most common serious infection in 2015–2016. Several patient and hospital factors are associated with health care utilization and mortality in serious infection hospitalization in vasculitis.