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In-hospital falls can result in substantial morbidity and mortality and were declared “never events” by the Centers for Medicare & Medicaid Services in 2008. Interventions that were intended to reduce the incidence of falls based on patient risk factors have not been successful in the acute inpatient setting. We hypothesized that a systems-based fall-prevention program targeting high-risk situations would result in fewer falls with injury.Falls that occurred in the prospective postintervention period were reviewed in real time with use of a clinical database that could be accessed by all physicians, nurses, aides, and therapists. Analysis of the hospital setting, patient factors, and circumstances associated with all falls occurring on the hospital’s orthopaedic ward were evaluated during the preintervention study period. On the basis of the findings from this audit, four systems-based interventions were implemented. Prospective analysis of these interventions was then conducted. All falls were tracked by means of the clinical database and reviewed by the study investigators. The rates of falls with injury and total falls in the preintervention and postintervention periods were compared.The preintervention study period (May 1, 2007, to September 28, 2008) represented 11,082 patient days, during which time the fall with injury rate and total fall rate were 1.17 and 4.24, respectively, per 1000 patient days. The postintervention study period (September 29, 2008, to May 1, 2010) represented 12,267 patient days, during which time the fall with injury rate and the total fall rate were 0.41 and 2.53, respectively, per 1000 patient days. The reductions in the rates of falls with injury (p = 0.036) and total falls (p = 0.024) were significant.Utilization of a continuous quality improvement model to develop a systems-based fall-prevention program can be effective in reducing falls with injury and total falls in an acute inpatient setting. Despite a thoughtful, multidisciplinary, intensive approach to the problem, falls did occur. We believe that it is unrealistic to consider all falls to be preventable.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.