Aim of the work: To evaluate clinical effectiveness and safety of negative pressure wound therapy (NPWT) compared with advanced moist wound therapy (AMWT) (mainly hydrogels, tulle and alginates) for treatment of diabetic foot wounds. Patients and methods: This was a prospective randomized study conducted on (40) patients with chronic diabetic foot wounds who were divided into (NPWT) group through vacuum assisted closure (VAC)® System and (AMWT) group mainly hydrocolloids, tulle or alginates. The study evaluated treatment until day (112) or ulcer closure by any means. The primary end point was incidence and median time of complete wound closure by either surgery or secondary intention. Wound assessment entailed wound area, progress of granulation tissue, infection, need for debridement, discharge and pain. Results: A significantly greater percentage of (NPWT) wounds (60%, 12 of 20) achieved complete closure than (AMWT) wounds (30%, 6 of 20) (P=0.033). Median time to complete wound closure was (76 days) for (NPWT) and (91 days) for (AMWT) (P =0.024). Median time to (76-100%) granulation was significantly shorter in (NPWT) (50 days) than in AMWT patients (88 days) (P = 0.0001). Conclusion: NPWT is as safe as and more efficacious than AMWT for the treatment of diabetic foot wounds.