Chronic wounds are characterized by a long inflammatory phase that hinders regenerative wound healing. The purpose of this prospective case series was to evaluate how a physiologically relevant concentration of an autologous platelet-rich plasma (PRP) gel affects initial wound healing trajectories of chronic, nonhealing wounds of various etiologies and in different care settings. Using convenience sampling methods, 49 patients (average age: 60.6 years, SD 14.7) with 65 nonhealing wounds (mean duration 47.8 weeks, range 3 to 260) at eight long-term acute care (LTAC) hospitals and three outpatient foot or wound clinics who were prescribed PRP gel for their nonhealing wound were enrolled. The majority of patients had low albumin, hematocrit, and/or hemoglobin levels. After wound assessments and measurements were obtained and the gel prepared, a skin barrier was applied to the periwound skin and the gel applied and protected with cover dressings. The most common wounds were pressure ulcers (n = 21), venous ulcers (n = 16) and diabetic foot ulcers (n = 14). Mean wound area and volume were 19 cm2 (SD 29.4) and 36.2 cm3 (SD 77.7), respectively. Following a mean of 2.8 (SD 2.4) weeks with 3.2 (SD 2.2) applications, reductions in wound volume (mean 51%, SD 43.1), area (39.5%, SD 41.2), undermining (77.8%, SD 28.9), and sinus tract/tunneling (45.8%, SD 40.2) were observed. For all wound etiologies, 97% of wounds improved. The results of this study suggest the application of this PRP gel can reverse nonhealing trends in chronic wounds.