Lipedema is a disproportional obesity for which evidence-based treatment is not currently available. We studied whether complete decongestive physiotherapy (CDP) alone or combined with intermittent pneumatic compression (IPC) could improve the treatment outcome in women with lipedema using a prospective, randomized trial. Eleven patients received CDP (60 min) and thirteen CDP (30 min) plus IPC (30 min) once daily in a 5-day-course. Subsequent to drainage, all subjects received multilayered compression bandaging, physical exercise and skin care. Treatment efficacy was evaluated by limb volume reduction. Both groups achieved significant reductions in mean lower extremity volume (p < 0.05). The addition of IPC is safe, although it provides no synergistic benefit to CDP in leg volume reduction under these study conditions.