INTRODUCTION: The role of rib fixation (RF) in flail chest is debated, and guidelines conditionally recommend RF in highly selected patients. Patients with cardiopulmonary disease (CPD) have traditionally not been deemed surgical candidates. We hypothesize that RF would benefit even high-risk patients with CPD. METHODS: Adult patients with isolated flail chest and CPD were identified from the Trauma Quality Improvement Program database (2016-2018). Hospital transfers, patients dead within 72 h, penetrating mechanism, concomitant thoracic aortic injury or cancer were excluded. Primary outcome was in-hospital mortality. Secondary outcomes were in-hospital complications, ventilator days, need for tracheostomy, and length of stay. RF patients were propensity score matched (1:1) to non-operative management (NOM) patients. Multivariate regression identified independent risk factors for outcomes. RESULTS: In this 3 year period, 4614 patients were admitted with flail chest and history of CPD. After exclusions and propensity matching, 544 (12%) underwent analysis (RF n = 272, NOM n = 272). RF patients had a lower mortality compared to NOM patients (1.8% vs 5.5%, p = 0.023) but more likely to develop venous thromboembolic events (5.1% vs 1.85%, p = 0.036), prolonged ventilation (28.4% vs 15.1%, p <
0.001), and tracheostomy (15.4% vs 6.6%, p = 0.001). Multivariate analysis showed RF was independently associated with decreased mortality (OR 0.165, 95% CI 0.037-0.735, p = 0.018) while age >
85 years (OR 145.115, 95% CI 9.721-2166.262) and ventilator-associated pneumonia (OR 8.283, 95% CI 1.375-49.888) were associated with increased mortality. CONCLUSIONS: RF shows a survival benefit even in high-risk patients with CPD. Patient selection should be individualized but RF should not be excluded based solely on pre-existing conditions.