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The purpose of this study was to evaluate the impact of implementing evidence-based guidelines on smoking cessation in persons with spinal cord injuries and pressure injuries. We also evaluated the impact of smoking on pressure injury healing in this population.The sample population included 158 spinal cord–injured patients with pressure injuries (29 females and 129 males). There were 83 in the control group and 75 in the intervention group, with a mean age of 44 years in both groups. The research setting was an outpatient wound clinic located in a large medical center in the southeastern United States.A retrospective chart review was completed. Data were reviewed 6 months before and 6 months after implementation of the US Department of Health and Human Services Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We evaluated the number and size of wounds, achievement of smoking cessation, and demographic information.Forty-eight percent of the control group participants and 57% of the intervention group participants smoked cigarettes at baseline. Smoking cessation doubled with the use of the clinical practice guidelines (P = .03). Smokers presented with a greater number of pressure injuries than nonsmokers. They experienced a mean increase rather than reduction in wound size. Nearly half (45.5%) of the intervention group participants who desired to have surgery had it performed, compared with only 34.9% of the control group participants (P = .35).Our findings demonstrate a positive influence with use of clinical practice guidelines to help individuals stop smoking. Results also confirm findings of previous studies supporting the negative impact of smoking on pressure injury healing in persons with spinal cord injuries.