Objective.To quantify healthcare resource utilization (HRU), work loss, and annual direct and indirect healthcare costs among patients with systemic sclerosis (SSc) compared to matched controls in the United States.Methods.Data were obtained from a large US commercial claims database. Patients were ≥ 18 years old at the index date (first SSc diagnosis) and had ≥ 1 SSc diagnosis in the inpatient (IP) or emergency room (ER) setting, or ≥ 2 SSc diagnoses on 2 different dates in the outpatient (OP) setting between January 1, 2005, and March 31, 2015; continuous enrollment was required during the followup period (12 months after the index date). Individuals with no SSc diagnoses were matched 1:1 to patients with SSc. Wilcoxon signed-rank and McNemar tests were used for comparisons and regressions with generalized estimating equations for adjusted OR (aOR) and incidence rate ratios (IRR) between 2 cohorts.Results.There were 2192 pairs of patients with SSc and matched controls included (mean age 57.6 yrs; 84.3% female); of these, 233 were eligible for work loss/indirect cost analyses. Compared to matched controls, patients with SSc had significantly higher HRU and costs during the 1-year followup period, IP admissions (adjusted IRR = 2.4), IP hospitalization days (adjusted IRR = 3.1), ER visits (adjusted IRR = 2.0), OP visits (adjusted IRR = 2.3), and days of work loss (adjusted IRR = 2.6). The adjusted difference in annual direct and indirect costs was US$12,820 and $3103, respectively (all p < 0.0001).Conclusion.Patients with SSc had a high direct and indirect economic burden postdiagnosis.