To assess whether systemic sclerosis (SSc) is associated with total knee arthroplasty (TKA) outcomes. We used the 1998-2014 US National Inpatient Sample. We conducted multivariable-adjusted logistic regression analyses to examine the association of a diagnosis of SSc with post-TKA in-hospital complications (implant infection, revision, transfusion, mortality) and healthcare utilization (hospital charges, hospital stay, non-home vs. home discharge). Odds ratios (OR) and 95 % confidence intervals (CI) were calculated. Our cohort included 8,123,388 people without SSc and 3894 people with SSc. In multivariable-adjusted analyses, compared to people without SSc, people with SSc had higher odds of transfusion, hospital stay > 3 days and non-home discharge with higher OR of 1.42 (95 % CI, 1.20, 1.69), 1.29 (95 % CI, 1.11, 1.49), and 1.29 (95 % CI, 1.11, 1.49), respectively. No differences were seen in revision, 0.68 (95 % CI, 0.10, 4.69) or hospital charges above the median, 1.01 (95 % CI, 0.70, 1.46). Differences in implant infection or mortality were not estimable, since none of the patients with SSc had implant infection or died. Sensitivity analyses that adjusted the main analysis additionally for hospital-level variables confirmed study findings with minimal or no attenuation of OR. SSc was associated with higher risk of transfusion and increased healthcare utilization after TKA. Future studies should examine if interventions can address modifiable factors to further optimize these outcomes.Key Points• Systemic sclerosis was independently associated with higher healthcare utilization after TKA.• The adjusted odds of transfusion was higher in people with systemic sclerosis compared to those without systemic sclerosis who underwent TKA.