Chronic lower extremity lymphedema is a debilitating, progressive disorder characterized by pathological lymphatic fluid accumulation, resulting in persistent swelling, discomfort, restricted mobility, and heightened infection susceptibility. Intermittent pneumatic compression (IPC) therapy has emerged as a promising adjunctive strategy designed to enhance lymphatic flow, reduce edema, and improve patient-reported outcomes. This prospective, single-arm cohort study enrolled adults aged 18 to 75 years diagnosed with Stage II or III lower extremity lymphedema, verified via lymphoscintigraphy. Participants received IPC therapy utilizing an advanced 8-chamber peristaltic device, calibrated to 80 mmHg, administered for 60 minutes, three times weekly, across six months. Primary outcomes included limb volume reduction assessed through optoelectronic perometry, pain reduction measured by the Visual Analog Scale (VAS), and quality of life changes evaluated via the Lymphedema Quality of Life Inventory (LyQLI). At six months, a mean limb volume reduction of 28.7% (p < .001) was achieved, with 72% of participants maintaining >25% reduction at twelve months. Pain intensity decreased by 54.8% (p < .001), while LyQLI scores indicated significant improvement across physical, emotional, and functional domains (+28–32%, p < .01). IPC therapy was well-tolerated with minimal adverse events. These findings affirm IPC's long-term efficacy and safety, supporting its integration into multidisciplinary lymphedema care to achieve sustained anatomical and quality-of-life improvements.