Deep and tunneling wounds are a challenge to apply and maintain most advanced wound dressings to promote effective healing. An autologous whole blood clot is a topical treatment and has been found to be safe and effective in healing cutaneous wounds. The active coagulation whole blood (ACWB) clot treatment, using the patient's own blood, is used to treat deep and tunneling wounds, by mixing the blood with coagulation components and applying it into the wound cavity allowing the clot to re-form inside the wound. We aimed to explore ACWB treatment in hard-to-heal wounds. 5 patients with multiple comorbidities, exhibiting surgical abdominal wound, chronic pilonidal sinus, stage 4 sacral pressure ulcer with exposed bone, post-amputation surgical site wound, and non-healing wound dehiscence at the site of a prior hip replacement, were all treated with the ACWB clot treatment. Complete wound healing was observed in 4/5 cases. In the fifth case, there was a 70% reduction in the depth and surface area of the abdominal surgical wound. The ACWB treatment was found to be effective in deep wounds with cavities and exposed structures. ACWB, in its flowable form, can effectively provide coverage of the deepest interstices of the wound's cavities by virtue of its liquid properties, forming a fibrin matrix, mimicking the role of the extracellular matrix. The flowable formulation of ACWB treatment safely and efficiently provides coverage of the entirety of the wound surface to improve the time and process of complex wound surface healing.