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Nitric oxide is an endogenous gas released by endothelial cells that induces vasodilatation and plays other important roles in the wound-healing process. Nitroglycerin preparations are liberators of nitric oxide. Podiatric physicians have used nitroglycerin paste and patches on patients in an attempt to increase perfusion to the foot. However, the drug’s efficacy seems to be largely anecdotal. A prospective, randomized, placebo-controlled, double-blind study was conducted to investigate the efficacy of a nitroglycerin patch in locally increasing perfusion to the foot. Twenty-two healthy subjects were randomly assigned to either a drug group (nitroglycerin patch, 0.2 mg/h) or a placebo group (adhesive patch without active ingredient). The patch was applied to the plantar arch of the foot. Objective and subjective measures were then used to detect changes in perfusion to the foot after a 2-hour experimental period. The objective measures, cutaneous thermometry and photoplethysmography, found no significant measurable difference in perfusion to the foot between the drug and placebo groups (P > .05). A subjective questionnaire used to assess changes in temperature or sensation detected by the subject yielded similar results. Thus a nitroglycerin patch dose of 0.2 mg/h showed no measurable ability to increase perfusion to the foot. Further research is needed to validate the indications for this therapy. (J Am Podiatr Med Assoc 96(4): 318–322, 2006)