PURPOSE: The purpose of this study was to assess the level of matrix metalloproteinase-8 (MMP-8) and wound-healing outcome measures (length, width, and depth, exudate amount, and tissue type) in pressure injuries (PIs) of spinal cord-injured patients treated with negative pressure wound therapy (NPWT) using a novel negative pressure device versus PI treated with wet to moist gauze (conventional wound care). DESIGN: Randomized controlled trial. SUBJECTS AND SETTING: Forty-four spinal cord-injured patients with stage 3 and 4 sacral PI participated in the study. The study setting was the Department of Orthopedic Surgery at King George's Medical University, in Lucknow, India. METHODS: Twenty two subjects were randomly allocated to undergo NPWT via a novel negative pressure device, and 22 participants received conventional wound dressing (wet to moist gauze dressings). Pressure injuries were treated for 9 weeks or until wound closure. Levels of MMP-8 were analyzed in the tissues of PIs at weeks 0, 3, 6, and 9 by enzyme-linked immunosorbent assay. RESULTS: Significantly lower levels of MMP-8 were observed in the NPWT group at week 6 and week 9. There were no significant changes in the length and width of PIs between the groups till week 3. Significant reduced length and width were observed in PIs of patients in the NPWT group at week 6 (P = .04) and week 9 (P = .001). Similarly, significant reduction in the depth of PIs was observed in the NPWT group at week 9 (P < .05). At the end of 9 week, levels of MMP-8 showed a positive correlation with reduction in the length, width, and depth of PIs in the NPWT group while in the conventional dressing group, negative correlation was observed in association with MMP-8 and the length, width, and depth of PIs. Exudate levels were significantly lower in the NPWT group compared with the conventional dressing group from week 3 (2.96 ± 0.21 vs 2.62 ± 0.49); this difference persisted through week 9 (1.35 ± 0.75 vs 0.14 ± 0.35). Conversion of slough into red granulation tissue was significantly higher in the NPWT group after week 6 (P = .001). CONCLUSION: Reduced levels of MMP-8 and an increased rate of healing were found in patients allocated to treatment with a novel negative pressure device as compared to wet to moist gauze conventional dressing. The novel NPWT device used in this study reduced exudate production and enhanced the rate of formation of red granulation tissue.