Background: Burn injuries are a major global health issue, causing significant morbidity and mortality. Negative-pressure wound therapy (NPWT) is a common treatment that aids fluid drainage and enhances blood flow, thereby promoting wound healing. However, its effects on wound healing parameters like fibroblast growth factor-2 (FGF2) and platelet-derived growth factor (PDGF) in deep dermal burns are not fully elucidated. This study aimed to compare NPWT with conventional treatments, namely 0.9% sodium chloride (NaCl) and silver sulfadiazine (SSD), in terms of their effects on FGF2 and PDGF levels in burn wounds. Methods: Seventy-two fresh tissue samples from Yorkshire pig deep dermal burn models were divided into three treatment groups: NPWT, NaCl, and SSD. Wounds were photographed and observed macroscopically. Tissue samples were collected on days 3, 7, 14, and 21 and analyzed using enzyme-linked immunosorbent assay for further statistical analysis. Results: Macroscopic observation indicated better epithelialization and granulation in the NPWT group, with minimal wound contraction. Although differences across the treatment groups were insignificant, NPWT maintained higher and more stable FGF2 levels, peaking on days 7 and 21 (780.62±353.88 ng/mL and 504.31±254.25 ng/mL), with significant delta (Δ) value increases in the later stages (P=0.042), which were not observed in the NaCl and SSD groups. PDGF concentrations showed insignificant differences across all treatment groups, with notable delta changes in the SSD group (P=0.018). Conclusion NPWT demonstrated superior wound healing performance compared to conventional treatments. In addition to favorable macroscopic findings, NPWT potentially maintained FGF2 levels throughout the wound healing process.