OBJECTIVES: The progressive decline in interstitial lung disease associated with non-scleroderma connective tissue disease (ILD-NSCTD) is linked to poor prognosis and frequently results in respiratory failure. Lung transplantation (LTx) offers a viable treatment option, yet its outcomes in ILD-NSCTD remain contentious, particularly across different subtypes. METHODS: This retrospective cohort study included patients with idiopathic pulmonary fibrosis (IPF) (n=11,610) and ILD-NSCTD (n=610) listed in the United Network for Organ Sharing (UNOS) database who underwent lung transplantation between May 5, 2005, and December 31, 2022. We used the Kaplan-Meier method to evaluate cumulative survival rates and logistic regression to assess the risk of post-operative complications. RESULTS: Compared to IPF patients, those with ILD-NSCTD are generally younger, with a lower proportion of male and white patients. After propensity matching, overall survival rates remained similar between the groups (log-rank, p=0.953). However, ILD-NSCTD was associated with a significantly higher risk of post-operative stroke (adjusted OR 1.75, 95% CI 1.12-2.74, p=0.015) and longer post-operative hospital stays (p<
0.001). Subgroup analyses yielded consistent results. Finally, infection was identified as the leading cause of death. CONCLUSIONS: Compared to IPF, patients with ILD-NSCTD have a significantly higher risk of post-operative stroke and extended hospital stays, potentially due to complications inherent to ILD-NSCTD. However, the underlying causes of these outcomes remain unclear. Despite these differences, short-term and long-term survival rates are comparable between the two groups, with consistent findings across various ILD-NSCTD subgroups. Therefore, ILD-NSCTD should not be regarded as a relative contraindication for lung transplantation. Nonetheless, the influence of extra-pulmonary complications in ILD-NSCTD patients requires further investigation.