Abstract Background: Foot infections are common in patients with diabetes and are associated with high morbidity and risk of lower extremity amputation. After surgical debridement, wound related complications as infection, secondary or major amputation are very common compared to non-diabetic pa-tients. Negative pressure wound therapy (NPWT) is a new wound care therapy and present an effective tool in the management of diabetic foot wound. Aim of Study: To compare and evaluate safety and clinical efficacy of negative pressure wound therapy compared to standard moist wound therapy (SMWT) in the treatment and management of diabetic foot wound. Patients and Methods: This is a cohort study involving 40 patients with active diabetic foot wound, in a high-volume tertiary referral vascular center. The study included patients attending Ain Shams University hospitals and Gamal Abdel Naser Hospital, both as in-patients and on out-patient basis They were divided into 2 groups: 20 patients (group A) were prescribed NPWT, and the other 20 patients (group B) received SMWT. Comparison between the two groups according to time to full granulation tissue, infection, number of sessions of debridement and limb salvage. Results: Patients treated with NPWT in group A showed earlier full granulation tissue in 10% of patients after 2 weeks, 68% after 4 weeks and 100% after 8 weeks, compared to 0% of patients treated with SMWT after 2 weeks, 21% after 4 weeks and 83% after 8 weeks, with a significant difference after 4 weeks (p-value 0.003). No significant difference between the two groups as regard as wound related complications. Conclusion: According to our study results, we concluded that NPWT has a significant effect on acceleration and pro-motion of granulation tissue. We suggest that NPWT is most appropriate for deep, cavitary and full thickness wound which helps an early closure of wounds. Also, NPWT is safe as SMWD regarding wound related complication such as wound infection, the need of surgical debridement or amputation with no significant difference.