8040 Background: Few studies have investigated the correlation of smoking history with pathogenic germline variants (PGVs) in patients diagnosed with lung cancer. With emerging opportunities for PGVs in DNA damage-repair (DDR) genes to inform precision therapies, we investigated the prevalence of PGVs in patients with lung cancer, stratified by smoking status. Methods: Germline genetic testing (GGT) (Invitae Corp.) and insurance claims (Komodo Healthcare MapTM) data were reviewed for 14,317 patients with an ICD code for lung cancer from 2015-2023 and hereditary cancer GGT of ≥ 10 genes. PGV rates were assessed overall, in DDR genes and in lung cancer related genes. Smoking history was defined by ICD codes. Number of genes tested varied per ordering clinician preference. Clinically actionable PGVs were defined as those associated with clinical management recommendations or trial eligibility per current standard of care guidelines. Chi-square tests were used with significance set to p < 0.05. Results: The cohort was predominantly female (70.9%), white (65.7%), and over half had a history of smoking (57.1%). PGVs in 73 known cancer-risk genes were identified in 1,804/14,317 (12.6%) patients. Frequencies of PGV were 12.6% (1,026/8,175) in patients with smoking history compared to 12.7% (778/6,142) in those with no reported smoking history. There was no statistically significant difference in DDR gene, TP53, or EGFR PGV rates for patients with or without smoking history (p > 0.05). Mean (SD) age of lung cancer diagnosis was significantly younger for patients with a history of smoking and DDR PGVs (61 (11)) compared to those with negative results (62 (12), p = 0.005). There was no significant difference in age of diagnosis between patients with no smoking history and DDR PGVs (60 (12)) and those with negative results (59 (13), p = 0.888). PGV rates by clinician-reported ancestry: Black/African-American, 9%; Asian or Pacific Islander, 11%; Hispanic, 12%; White, 13%. Among genes with > 1,000 patients tested, PGVs were most common in BRCA2 (2.2%), CHEK2 (2.0%), ATM (1.6%), SPINK1 (1.6%), and BRCA1 (1.2%). Conclusions: In 14,317 patients with lung cancer, 12.6% had PGVs. There was no significant difference in enrichment of PGVs in DDR genes when patients were stratified by reported smoking history, suggesting the enrichment of these genes is independently associated with lung cancer. The age of onset for patients with DDR gene PGVs varied with smoking history, suggesting that risk conferred by these PGVs could be additive to smoking risk. These data reinforce prior studies supporting consideration of GGT for all patients with lung cancer, independent of age or reported smoking history.