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Background: Pressure ulcers are common in many care settings, with adverse health outcomes and high treatment costs. We evaluated the cost-effectiveness of evidence-based strategies to improve current prevention practice in long-term care facilities., Methods: We used a validated Markov model to compare current prevention practice with the following 4 quality improvement strategies: (1) pressure redistribution mattresses for all residents, (2) oral nutritional supplements for high-risk residents with recent weight loss, (3) skin emollients for high-risk residents with dry skin, and (4) foam cleansing for high-risk residents requiring incontinence care. Primary outcomes included lifetime risk of stage 2 to 4 pressure ulcers, quality-adjusted life-years (QALYs), and lifetime costs, calculated according to a single health care payer's perspective and expressed in 2009 Canadian dollars (Can$1 = US$0.84)., Results: Strategies cost on average $11.66 per resident per week. They reduced lifetime risk; the associated number needed to treat was 45 (strategy 1), 63 (strategy 4), 158 (strategy 3), and 333 (strategy 2). Strategy 1 and 4 minimally improved QALYs and reduced the mean lifetime cost by $115 and $179 per resident, respectively. The cost per QALY gained was approximately $78 000 for strategy 3 and $7.8 million for strategy 2. If decision makers are willing to pay up to $50 000 for 1 QALY gained, the probability that improving prevention is cost-effective is 94% (strategy 4), 82% (strategy 1), 43% (strategy 3), and 1% (strategy 2)., Conclusions: The clinical and economic evidence supports pressure redistribution mattresses for all long-term care residents. Improving prevention with perineal foam cleansers and dry skin emollients appears to be cost-effective, but firm conclusions are limited by the available clinical evidence.