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Introduction: Central Line-Associated Bloodstream Infections (CLABSIs) are preventable yet remain a major source of patient harm and hospital costs, increasing length of stay by up to 10 days and adding over $45,000 per case. Community hospitals often face unique challenges in sustaining best practices compared to larger academic centers. Methods: Saint Agnes Medical Center launched a year-long multidisciplinary QI project (Jan–Dec 2024) using the Plan-Do-Study-Act model. Interventions included simulation-based inserter training, standardized insertion checklists, and a nurse-led “stop-the-line” policy. Midline catheter use increased as a first-line alternative when appropriate, and external jugular access was adopted by the crisis team. Peripheral vasopressors were introduced using evidence-based protocols with close monitoring for complications such as limb ischemia. Maintenance bundles included CHG bathing, dressing change competency, and daily line necessity reviews. Transparency was supported via unit-level dashboards, monthly feedback, and incentive-based recognition. Results: Total CLABSIs declined from 22 to 8 (64%), and central line days dropped 15%. The hospital-wide standardized infection ratio (SIR) improved from 1.24 to 0.83 (95% CI: 0.31–1.46). In the ICU, CLABSIs fell from 14 to 3 (79%), with a line day reduction of 24%. The ICU SIR improved from 1.81 to 0.51 (95% CI: 0.00–1.18), significantly outperforming national benchmarks. The introduction of midlines and peripheral vasopressors contributed to reduced central line use while maintaining patient safety. Conclusions: This project demonstrates that community hospitals can achieve substantial reductions in CLABSI through low-cost, multidisciplinary interventions focused on standardization, empowerment, and evidence-based vascular access. These strategies are scalable and align with national guidelines to enhance patient safety.