This chapter presents a comprehensive guide for the practical application of negative pressure wound therapy (NPWT) with the technique of instillation of a chosen topical solution into the foam dressing to interface with the wound bed, either by a manual process or an automated pump. This new process enhances this wound healing technology. Through a systematic and detailed approach, this chapter provides healthcare practitioners with a framework for effectively utilizing NPWT with instillation beginning with appropriate patient selection, wound bed preparation, precise techniques for application, selection of appropriate instillation solutions, and device management. We would like to emphasize our focus on a patient-centered approach, addressing considerations for comfort, safety, and optimal wound healing. Practical tips, troubleshooting strategies, and illustrative case studies augment the instructional material, facilitating comprehension and skill acquisition. By synthesizing evidence-based practices with clinical expertise, this chapter equips healthcare professionals with the knowledge and proficiency necessary to proficiently administer NPWT with instillation, thereby advancing the standard of care for patients with complex wounds. V.A.C.® Veraflo™ Therapy, a form of negative pressure wound therapy with instillation, was introduced by KCI (Kinetic Concepts, Inc.) in the United States in 2012. This technology combines traditional NPWT with automated delivery and removal of topical wound solutions to help cleanse the wound bed and remove infectious material. This author team of acute care surgeons and wound care nurses has over 8 years of use of this product and has placed 10,638 NPWT dressings in the last 6 years at our facility. Our experience with instillation has increased from 12% in 2017, and more than 40% of the applied wound NPWT dressings were instilled with solution. We fully acknowledge that the increase in clinical skills and application processes has gone hand in hand with this new technology.