Objectives: The aim of this study was to perform an updated systematic review and meta-analysis to assess the clinical efficacy, safety, and cost-effectiveness of negative-pressure wound therapy (NPWT) in the treatment of diabetic foot ulcers (DFUs). Methods: We searched the Cochrane Library, MEDLINE, EMBASE, Ovid, and Chinese Biological Medicine databases up to June 30, 2016. We also manually searched the articles from reference lists of the retrieved articles, which used the NPWT system in studies of vacuumassisted closure therapy. Studies were identified and selected, and two independent reviewers extracted data from the studies. Results: A total of eleven randomized controlled trials, which included a total of 1,044 patients, were selected from 691 identified studies. Compared with standard dressing changes, NPWT had a higher rate of complete healing of ulcers (relative risk, 1.48; 95% confidence interval [CI]: 1.24-1.76; P<0.001), shorter healing time (mean difference, -8.07; 95% CI: -13.70- -2.45; P=0.005), greater reduction in ulcer area (mean difference, 12.18; 95% CI: 8.50-15.86; P<0.00001), greater reduction in ulcer depth (mean difference, 40.82; 95% CI: 35.97-45.67; P<0.00001), fewer amputations (relative risk, 0.31; 95% CI: 0.15-0.62; P=0.001), and no effect on the incidence of treatment-related adverse effects (relative risk, 1.12; 95% CI: 0.66-1.89; P=0.68). Meanwhile, many analyses showed that the NPWT was more cost-effective than standard dressing changes. Conclusion: These results indicate that NPWT is efficacious, safe, and cost-effective in treating DFUs. [ABSTRACT FROM AUTHOR]