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Introduction: The negative pressure wound therapy (NPWT) is an effective local treatment method of many non-healing wounds. NPWT is routinely used for inpatient treatment in the Czech Republic; however, no clinical data is available for systematic outpatient treatment., Methods: The prospective non-randomized study was used to compare the clinical impact and cost-effectiveness of diabetic leg-ulcer and foot-ulcer negative pressure treatment in outpatient and inpatient settings. The aim of the study was to assess the effectiveness of outpatient NPWT on the basis of wound bed evaluation, to detect and quantify pre-expected reductions in the total costs of the therapy, and to compare the efficacy of both treatment options. Enrolled subjects included inpatients (n=36, NPWT systems RENASYS GO or PICO) and outpatients (n=28, PICO system). NPWT was concluded when the wound bed had been totally covered by granulation tissue, or when serious health problems occurred. We monitored the ulcer area, wound bed trait, number of NPWT dressing changes, length of NPWT, intensity of pain (VAS scale), presence of complications, and treatment costs., Results: We found comparable clinical efficacy of outpatient (n=28)/inpatient (n=36; statistically non-significant differences in healing of ulcers verified based on wound bed development and reduction of ulcer areas in time) NPWT, the same risk of complications associated with NPWT (statistically non-significant differences in the function of both technologies and in complications developed during follow-up) as well as similar long-term results (statistically non-significant differences in the count of amputations). The total costs for outpatient wound treatment were statistically significantly lower (EUR 600 versus EUR 1300, p=0.001), and so were the average one-day-NPWT costs (EUR 30 versus EUR 120, p=0.001)., Conclusion: We demonstrated that outpatient diabetic-foot-ulcer NPWT provided the same clinical efficiency as inpatient NPWT, while outpatient NPWT was less expensive, less painful and better tolerated than inpatient NPWT.