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Background: Lung transplantation (LT) demand outpaces supply. Consequently, extended criteria for donor selection are used, resulting in LT from donors with a history of substance use (SU). The aim of this study is to assess the association between donor SU and short-term LT outcomes. Methods: We obtained recipient and donor data for LTs performed between January 2014 to January 2019 from electronic health records and the United Network for Organ Sharing (UNOS) database. We defined SU as cigarette/e-cigarette smoking, illicit SU (cannabis, cocaine, opioids, amphetamines), or heavy alcohol use (2+ alcoholic drinks per day). Our primary outcome was late high-grade primary graft dysfunction (PGD), which we defined as grade 2-3 PGD between 48-72 hours post-LT. Secondary outcomes included mechanical ventilation (MV) hours, intensive care unit (ICU) length of stay (LOS), hospital LOS, number of bronchoscopies, cumulative acute rejection (CAR) score in the first year after LT, and overall survival (OS). Results: A total of 352 LTs were included in this study. On multivariable regression, we found that any donor cigarette smoking was associated with increased odds of late high grade PGD (p=0.021), while any donor cannabis use was associated with reduced odds of late high grade PGD (p=0.002). There was no association between any donor SU and secondary outcomes. Conclusions: Donor cigarette use was associated with higher risk for PGD. Our findings may suggest a history of donor cannabis use and other illicit SU are not associated with PGD or worse OS.