Introduction. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) of topical solutions is a useful method for managing difficult-to-heal wounds, particularly for contaminated chronic ulcers. Most patients with chronic ulcers are affected by several pathologies that systemically impair wound healing; local slough and bacteria further increase the risk of treatment failure. Case Report. A 57-year-old male with obesity, diabetes, and heart disease presented with infected venous leg ulcers of 2 years’ duration. The patient came to the authors’ attention after unsuccessful treatment with advanced wound care dressings. The patient underwent surgical debridement and application of NPWTi-d with saline solution (settings: -100 mm Hg, 32 mL of instilled volume, 10-minute dwell time, and 2-hour cycle length) for 16 days. This resulted in good granulation tissue formation on the wound bed, so a meshed skin graft was used to cover the wound. In order to improve the skin graft take, the authors dressed it with polyvinyl alcohol foam connected to a traditional NPWT device (settings: -75 mm Hg, continuous pressure) for 1 week. After this period, complete wound healing was achieved, and the wound remained closed and stable upon follow-up. Conclusions. In the authors’ opinion, NPWTi-d of topical solutions can be very useful in order to enhance debridement and reduce bacterial load. This kind of treatment allowed the authors to obtain a very good wound bed, and its application was very quick and easy to use, with no adverse events.