278 Background: Surgical resection is the most important curative modality for patients with lung cancer, with long-term OS influenced by both surgical quality and cancer biology. We compared surgical care and outcomes over 4 eras in the population-based Mid-South Quality of Surgical Resection (MS-QSR) cohort, an ongoing regional surgical and pathologic quality improvement (QI) dissemination and implementation project. Methods: We implemented a surgical lymph node collection kit and a novel pathology gross dissection method across 12 hospitals encompassing >95% of lung cancer resections in 5 contiguous Dartmouth Hospital Referral Regions. We analyzed the MS-QSR cohort at 5-year intervals characterized by stepped-wedge implementation of specific QI interventions: Era 1 (2004-2008; baseline, no QI), Era 2 (2009-2013; quality feedback, surgical QI pilot), Era 3 (2014-2018; surgical QI implementation), and Era 4 (2019-2023; combined surgical QI and pathology QI implementation). We used standard statistical methods to compare surgical quality; Kaplan-Meier plot, log-rank test, and Cox proportional hazards model with Era 1 as reference to compare OS across eras. Results: Of 7240 resections, 14%, 31%, 29%, and 26% were performed in Eras 1-4, respectively (Table). Attainment of the stringent International Association for the Study of Lung Cancer (IASLC) definition of complete resection increased from 0% in Era 1 to 32% in Era 4; attainment of the American College of Surgeons Operative Standard 5.8 (ACS_OS 5.8), the current US definition of surgical quality, improved from 4% in Era 1 to 67% in Era 4; 120-day mortality rate decreased from 10% to 4% (p<0.0001 for all comparisons). With median follow-up of 4.7, 5.5, 5.6, and 2 years for Eras 1-4, 3-year OS rates were 60%, 64%, 70%, and 79%; 5-year OS rates were 48%, 52%, 58%, and 70%, respectively (p<0.0001). The Hazard Ratio (HR) for mortality decreased from 0.91 (95% CI: 0.8-0.99) in Era 2 to 0.49 (95% CI: 0.43-0.56) in Era 4. Conclusions: Surgical quality and OS sequentially improved in this diverse, high-risk population-based Mississippi Delta surgical resection cohort. We are evaluating the full range of factors associated with this striking OS improvement. Ongoing work is exploring biologic correlates to this improvement. Variable Era 1 N= 988 Era 2 N=2235 Era 3 N=2107 Era 4 N=1910 Median age (Q1, Q3) 68 (62, 74) 68 (62, 74) 68 (61, 74) 68 (61, 74) Male sex (%) 514 (52%) 1234 (55%) 1082 (51%) 977 (51%) Black race 221 (22%) 416 (19%) 450 (21%) 451 (24%) Attained ACS_OS 5.8 40 (4%) 533 (24%) 1050 (50%) 1272 (67%) IASLC complete resectionUncertain completeness 0 (0%)930 (94%) 194 (9%)1932 (86%) 435 (21%)1594 (76%) 606 (32%)1227 (64%) 120-day mortality 100 (10%) 197 (9%) 139 (7%) 72 (4%) 5-year OS 48 (45-51) 52 (50-55) 58 (56-60) 70 (66-74) HR (95% CI) Reference 0.91 (0.83-0.99) 0.75 (0.69-0.83) 0.49 (0.43-0.56)