Objective: To study incidence, time-trends and outcomes of serious infections in scleroderma. Methods: We used the 1998-2016 U.S. National Inpatient Sample data. We examined the epidemiology, time-trends and outcomes of five serious infections (opportunistic infections (OI), skin and soft tissue infections (SSTI), urinary tract infection (UTI), pneumonia, and sepsis/bacteremia) in hospitalized people with scleroderma. We performed multivariable-adjusted logistic regression analyses to analyze independent association of factors with healthcare utilization (hospital charges, length of hospital stay, discharge to non-home setting), and in-hospital mortality. Results: There were 49,904,955 hospitalizations with serious infections in people without scleroderma and 61,615 in those with scleroderma. During 1998-2016, the most common serious infections in scleroderma were pneumonia (45%), sepsis (32%), SSTI (19%), UTI (3%) and OI (3%). In 2013-14, sepsis surpassed pneumonia as the most common serious infection; by 2015-16, sepsis was 1.8-times more common than pneumonia. Over the study period, hospital charges increased, while length of hospital stay and in-hospital mortality decreased, overall and for each serious infection. Multivariable-adjusted analyses showed that sepsis, age ≥80 years and Deyo-Charlson score ≥2 were associated with significantly higher odds of healthcare utilization and in-hospital mortality; and Medicare or Medicaid insurance payer, Northeast location, urban teaching or non-teaching hospital, and medium or large hospital bed size with significantly higher odds of healthcare utilization. Conclusions: Outcomes in people with scleroderma hospitalized with serious infections have improved over time, except higher hospital charges. Identification of factors associated with higher healthcare utilization and in-hospital mortality allows for developing interventions to improve outcomes.