OBJECTIVE: To examine the epidemiology/time-trends/outcomes of serious infections and type in people with vasculitis in the U.S. METHODS: We identified people with vasculitis hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections (SSTI), or opportunistic infections (OI) in the 1998-2016 U.S. National Inpatient Sample. We used adjusted logistic regression to examine the predictors of hospital stay >3 days, total hospital charges >median, discharge to non-home setting, and in-hospital mortality. RESULTS: We noted 111,345 serious infections in people with vasculitis (14% of all vasculitis hospitalizations). The mean age was 67.3 years, Deyo-Charlson comorbidity score was ≥2 in 54%, 37% were males, 67% white. Serious infection hospitalization rate per 100,000 NIS claims in 1998-2000 versus 2015-2016 (and increase) in people with vasculitis were as follows: Overall, 12.14 to 25.15 (2.1-fold); OI, 0.78 vs. 0.83 (1.1-fold); SSTI, 1.38 versus 2.52 (1.8-fold); UTI, 0.35 versus 1.48 (4.2-fold); pneumonia, 7.10 vs. 6.23 (0.9-fold); and sepsis, 2.53 vs. 14.10 (5.6-fold). Pneumonia was the most common serious infection (58%) in 1998-2000, versus sepsis (56%) in 2015-2016. Sepsis, older age, Deyo-Charlson index ≥2, urban hospital, or medium/large hospital bed size, were associated with higher healthcare utilization and in-hospital mortality; Northeast region, Medicare and Medicaid payer type were associated with higher healthcare utilization. CONCLUSIONS: Hospitalized serious infection rates are increasing in vasculitis, except pneumonia. Sepsis was the most common serious infection in 2015-2016. Several patient and hospital factors are associated with healthcare utilization and mortality in serious infection hospitalization in vasculitis.