Background: Operating room (OR) nurses are at high risk for work-related musculoskeletal disorders (WMSDs) due to physically demanding tasks and the use of heavy lead aprons. Objectives: This study evaluated the impact of a multidimensional ergonomic intervention on injury prevention awareness, compliance, and health outcomes among OR staff. Methods: A prospective quality improvement pilot study was conducted with 33 OR nurses. The intervention, based on the Health Belief Model and Human Factors Engineering, integrated ergonomic education with environmental modifications. Outcomes were assessed via questionnaires, field audits, and sick leave records at baseline, post-intervention, and 6-month follow-up. Results: Awareness scores improved from 68.7% to 98.8% (p < 0.001). Observational audits demonstrated a reduction in non-ergonomic actions from 2227 to 440 (mean deviations per nurse: 111.4 to 22.0, p < 0.001), with improvements sustained at 6 months. Annual sick leave cases decreased from three to one. Conclusions: A multifaceted real-world pilot intervention combining education with system-level engineering was associated with enhancing ergonomic compliance and reducing unsafe behaviors. This approach fosters the self-efficacy necessary for sustainable WMSD risk mitigation in high-intensity clinical settings.