This multicenter, retrospective study evaluated the wound healing and limb salvage outcomes over a 4-year period in 3,830 patients in 39 hospital-affiliated Wound Care Centers. These centers provide comprehensive outpatient wound care for chronic, nonhealing wounds. Two distinct outcomes were identified: (1) wound healing with comprehensive wound care (CWC) alone, and (2) wound healing with comprehensive wound care plus platelet releasate (CWC+PR). Data were analyzed with respect to healing and limb salvage in two groups: 1,019 patients who received CWC and 2,811 patients who received CWC+PR. Analysis of the standardized, customized database showed that overall healing rates were higher (p < .00001) and amputation rates were lower (p = .00005) in the CWC+PR group than in the CWC group. In addition, when healing rates were analyzed according to underlying condition, patients with all underlying conditions except autoimmune disorders showed higher healing rates in the CWC+PR group than in the CWC group. This study showed that patients treated with comprehensive wound care plus topical use of autologous platelet releasate had significantly higher rates of wound healing and increased limb salvage for most wounds than those treated with comprehensive wound care alone.