Introduction: Micronized cadaveric acellular dermal matrix (mADM) paste, which functions by filling vertical wound planes with acellular dermal matrix particles and gelatin suspension, is a novel option for the treatment of hard-to-heal wounds. We aimed to evaluate the clinical outcome of mADM paste used in conjunction with negative pressure wound therapy (NPWT) in the treatment of hard-to-heal wounds. Methods: This prospective clinical trial enrolled 20 patients with hard-to-heal wounds from January 2016 to January 2017. Wound healing was assessed at 1, 2, 3, and 4 weeks after treatment. Wound size and depth and patient satisfaction were recorded at each follow-up. Results: The area of the wound was measured in all study participants, which decreased from an average of 15.48 ± 22.38 cm 2 at the start of the study to 8.97 ± 17.73 cm 2 after 4 weeks, with a reduction rate of 59.10% ± 31.76% (P < 0.0001). Two weeks into the study, there was a significant decline in the wound depth compared with the previous week. Conclusion: mADM with NPWT provides effective wound healing. It is more comfortable for the patients and less timeconsuming for the nursing staff; thus, this treatment deserves a prominent place in the care of patients with hard-toheal wounds.