This study aimed to evaluate the efficacy of combining autologous platelet-rich plasma (PRP) with negative pressure wound therapy (NPWT) for the repair of pressure ulcers. We included 90 patients with pressure ulcers from General Technology Gemstone Flower Healthcare Jilin City Hospital of Chemical Industry between January 2021 and December 2023. Patients were randomly assigned to either a control group or an observation group, with 45 patients in each. The control group received NPWT alone, while the observation group received a combination of PRP and NPWT. Outcomes were compared between the groups, including clinical efficacy, wound recovery time (infection control time, wound healing time, hospital stay), levels of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, white blood cell count), pain scores (numerical rating scale), Pressure Ulcer Scale for Healing scores, and incidence of complications. The observation group demonstrated a total effective rate of 95.56% (43/45), significantly higher than the control group’s 80.00% (35/45) (P < .05). Additionally, the observation group had significantly shorter infection control times, wound healing times, and hospital stays (P < .05). Two weeks post-surgery, the observation group had significantly lower levels of C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, as well as reduced numerical rating scale and Pressure Ulcer Scale for Healing scores (P < .05). The incidence of complications was 6.67% (3/45) in the observation group compared to 33.33% (15/45) in the control group, with a significant difference (P < .05). Combining autologous PRP with NPWT significantly improves clinical outcomes, reduces inflammatory responses, decreases pain, accelerates wound healing, and lowers complication rates in patients with pressure ulcers.