BACKGROUND: Compression therapy is the most widely used treatment for venous leg ulcers and it was used in different forms for more than 400 years. Published healing rates of venous ulcers obtained with compression therapy vary widely from 40-95%. According to numerous studies, it has been suggested that the application of external pressure to the calf muscle raises the interstitial pressure resulting in improved venous return and reduction in the venous hypertension. Several risk factors have been identified to be correlated with the failure of venous leg ulcers to heal with compression therapy (longer ulcer duration; large surface area; fibrinous deposition present on >50% of the wound surface and an Ankle Brachial Pressure Index (ABPI) of <0.85. METHODS: An open prospective single-center study was performed in order to determine possible risk factors associated with the failure of venous ulcers to heal when treated with multi-layer high compression bandaging system for 52 weeks. In the study, 189 patients (101 women, 88 men; mean age 61 years) with venous leg ulcers (ulcer surface >5 cm(2); duration >3 months) were included. The study excluded patients with arterial disease (ABPI <0.8), heart insufficiency with ejection fraction (EF) <35, pregnancy, cancer disease, rheumatoid arthritis, and diabetes. Based on clinical opinion and available literature, the following were considered as potential risk factors: sex, age, ulceration surface, time since ulcer onset, previous operations, history of deep vein thrombosis, body mass index (BMI), reduction in calf circumference >3 cm during the first 50 days of treatment, walking distance during the day <200 meters, calf:ankle circumference ratio <1.3, fixed ankle joint, history of surgical wound debridement, >50% of wound covered with fibrin, depth of the wound >2 cm. RESULTS: Within 52 weeks of limb-compression therapy, 24 (12.7%) venous ulcers had failed to heal. A small ulceration surface (<20 cm(2)), the duration of the venous ulcer <12 months, a decrease in calf circumference of more than 3 cm, and emergence of new skin islets on >10% of wound surface during the first 50 days of treatment were favorable prognostic factors for ulcer healing. A large BMI (>33 kg/m(2)), short walking distance during the day (<200 m), a history of wound debridement, and ulcers with deepest presentation (>2 cm) were indicators of slow healing. Calf:ankle circumference ratio <1.3, fixed ankle joint, and reduced ankle range of motion were the only independent parameters associated with non-healing (P < .001). CONCLUSION: The results obtained in this study suggest that non-healing venous ulcers are related to the impairment of the calf muscle pump.