Introduction. Diabetic foot ulcers (DFUs) are slow to heal because of poor tissue vascularity and regenerative capacity, among various factors. Objective. In this study, the authors evaluate the efficacy of applying a paste formulation of acellular dermal matrix (ADM) to DFUs. Materials and Methods. Patients with Wagner grade 2 or 3 DFUs (N = 49) received either ADM paste (treatment group; n = 23) or conventional foam dressing (control group; n = 26). All chronic wounds were debrided and irrigated in an attempt to control infection. After paste application, mild compaction was undergone to fill ulcer cavities, and foam dressings were used to cover the surface to absorb any discharge. All DFUs were analyzed with regard to ulcer area, depth, progression, healing rate, and duration to complete healing. Results. At the 60-day primary outcome mark, 56.52% (13/23) of the DFUs in the treatment group were healed, compared with 23.08% (6/26) of DFUs in the control group. Mean rates of wound area resolution in the treatment and control groups were 74.17% ± 30.84% and 51.87% ± 32.81%, respectively (P < .05), with mean times to heal (within 60 days) of 13.54 ± 9.18 days and 21.5 ± 11.98 days, respectively (P < .05). There were no serious adverse events in either group, and no complications related to ADM paste application. Conclusions. The ADM paste effectively enhanced tissue regeneration, shortening ulcer duration and preventing associated complications, while eliminating the need for supplemental ulcer management procedures. The paste formulation of ADM provides a matrix for tissue ingrowth, promoting the healing of DFUs.