OBJECTIVE: To evaluate the clinical role of noncontact, low-frequency ultrasound therapy (MIST Therapy System; Celleration, Eden Prairie, Minnesota) in the treatment of chronic lower-extremity wounds. DESIGN: A retrospective observational study. SETTING: A multidisciplinary, vascular wound-healing clinic. PATIENTS: One hundred sixty-three patients who received MIST Therapy plus standard of care (treatment group) and 47 patients who received the standard of care alone (control group). INTERVENTIONS: All wounds in the control and treatment groups received the standard of wound care and were followed for 6 months. In the treatment group, MIST Therapy was administered to wounds 3 times per week for 90 days or until healed. MAIN OUTCOME MEASURES: Proportion of wounds healed and wound volume reduction. Rate of healing was also quantified using 1-way analysis of variance to determine the slope of the regression line from starting volume to ending volume, where a steeper slope indicates a faster healing rate. Outcomes were evaluated in all wounds and etiology-specific subgroups. MAIN RESULTS: A significantly greater percentage of wounds treated with MIST Therapy and standard of care healed as compared with those treated with the standard of care alone (53% vs 32%; P = 0.009). The slope of the regression line in the MIST arm (1.4) was steeper than the slope in the control arm (0.22; P = .002), indicating a faster rate of healing in the MIST-treated wounds. CONCLUSION: The rate of healing and complete closure of chronic wounds in patients improved significantly when MIST Therapy was combined with standard wound care.