Preventing wound infection and the development of resistant bacteria are important concerns in wound management. To determine if noncontact, nonthermal, low-frequency ultrasound therapy is effective in controlling wound bacterial colony counts, a series of four related experiments was conducted. First, ultrasound penetration in both wounded and intact skin was assessed in vitro. Compared to sham, noncontact ultrasound penetrated farther into both wounded (3 mm to 3.5 mm versus 0.35 mm to 0.50 mm) and intact (2.0 mm to 2.5 mm versus 0.05 mm to 0.07 mm, respectively) pig skin. Second, using an in vitro model to stain and count live/dead bacteria, 0% of sham treated and 33% of Pseudomonas aeruginosa, 40% of Escherichia coli and 27% of Enterococcus faecalis were dead after one ultrasound application. Minimal effects on methicillin-resistant Staphylococcus aureus and S. aureus were observed. Third, using an in vivo model, after 1 week, while differences between different bacterial species were observed, overall bacterial quantity decreased with ultrasound treatment (from 7.2 +/- 0.79 to 6.7 +/- 0.91 colony forming units per gram of tissue [CFU/g]) and silver antimicrobial dressings (from 7.2 +/- 0.79 to 5.7 +/- 0.6 CFU/g) but increased to 8.6 +/- 0.15 CFU/g for sham and 8.6 +/- 0.06 CFU/g for water-moistened gauze. Fourth, 11 patients (average age 60 years) with pressure ulcers containing bacterial counts >10(5) CFU/g of tissue received 2 weeks of noncontact ultrasound therapy. The quantities of seven bacterial organisms were reduced substantially from baseline to 2 weeks post treatment. None of the wounds exhibited signs of a clinical infection during the treatment period and no adverse events were observed. Taken together, these four studies indicate that noncontact ultrasound can be used to reduce bacterial quantity. Controlled clinical studies are warranted to ascertain the efficacy of this treatment and to further elucidate its effects on various Gram-negative and Gram-positive bacteria.