Background: Chronic lower limb wounds, such as diabetic and vascular ulcers, affect up to 2% of the global population, imposing high healthcare costs and a significant risk of amputation. Although nursing care and traditional treatments are fundamental, single-use portable Negative Pressure Wound Therapy PICO 7 system, has emerged as a cost-effective alternative. The objective of this study was to evaluate the effectiveness of PICO 7, compared to the usual treatment in chronic lower limb wounds or their dehiscence in amputations. Methodology: A randomized, controlled, open-label clinical trial was conducted at the Hospital Universitario de Toledo (2024–2026). The final analyzed sample consisted of 31 patients (Intervention Group, IG: 14; Control Group, CG: 17). Both groups followed the dynamic TIME strategy to standardize wound bed preparation. Primary variables included healing rate, healing time, wound area reduction, clinical safety (infections and adverse effects), pain levels, health-related quality of life, and physical activity. Statistical analysis was performed using SPSS v.28. Results: The IG showed a higher mean percentage reduction in wound size, although the between-group difference did not reach statistical significance. No infections were recorded in the IG. Regarding quality of life and physical activity, the CG showed a significant post-intervention decline, whereas the IG remained stable. A significant negative correlation was found between final wound size and hours of sleep, suggesting that wound reduction facilitates better rest. Conclusions: The PICO 7 system appears to be a safe and feasible alternative to conventional wound care. Favorable trends in wound area reduction should be interpreted cautiously given the lack of statistically significant between-group differences.