Summary: Background: Because of side effects like skin dryness and consecutive symptoms like itching the therapy of chronic venous insufficiency (CVI) with medical compression stockings (MCS) can lead to a diminished wear comfort and restricted compliance. Compression stockings with integrated skin care may have a positive influence on the skin hydration and moreover a positive effect on patients compliance. Patients and methods: In this monocentric, randomized prospective, controlled trial a below knee conventional MCS was compared to a medical compression stocking with integrated skin care (MCS-SC), interface pressure range 23–32 mmHg. Participants: 50 patients with CVI. Primary outcome: skin hydration. Secondary outcomes: transepidermal water loss, skin roughness, leg volume, interface pressure and questionnaires about quality of life and wear comfort. Results: In patients wearing MCS the skin moisture decreased (p = 0.021) and the skin roughness increased significantly (p = 0.001), whereas in patients wearing the MCS-SC skin moisture and skin roughness changed only slightly (n.s.). These protective effects of MCS-SC compared to MCS were most common in patients with CVI at stage 3 (p = 0.046), in male patients (p = 0.013) and patients with initial dry skin (p = 0.034). Both MCS reduced lower leg volume, MCS by 80 ml (p