With scrutiny from survey agencies (Centers for Medicare and Medicaid Services and state agencies) and potential litigation increasing, long-term care facilities must implement aggressive pressure ulcer prevention programs. However, cost-effective pressure ulcer prevention continues to be a challenge for most long-term care facilities, in part because limited research is available to guide their efforts. Two long-term care facilities (Facility A with 150 beds and Facility B with 110 beds) participated in a quasi-experimental study using retrospective and prospective study data to evaluate the effect of implementing a protocol of care to address the incidence of pressure ulcers. Retrospective study results showed a combined, cumulative, 5-month pressure ulcer incidence of 43% in Facilities A and B. Implementation of the comprehensive prevention program resulted in an 87% decrease in pressure ulcer incidence in Facility A (from 13.2% to 1.7% per month, P = 0.02) and a 76% decrease in Facility B (from 15% to 3.5% per month, P = 0.02). The average monthly cost of prevention for a high-risk resident was $519.73 (plus a one time cost of $277 for mattress and chair overlays). More than half ($277.15) of the monthly costs relates to labor; the most expensive item cost is for support surfaces. This study demonstrated that this comprehensive program resulted in a significant decrease in the incidence of pressure ulcers in two long-term care facilities. Because labor and support surface costs remain high, long-term care facilities are encouraged to use prevention intervention strategies based on risk stratification.