Objectives: Topical wound oxygen (TWO2) may help wound heating in the management of refractory venous ulcers (RVU). The aim of this study was to measure the effect of TWO2 on wound heating using the primary end-point of the proportion of ulcers heated at 12 weeks. Secondary end-points were time to full heating, percentage of reduction in ulcer size, pain reduction, recurrence rates and Quality-Adjusted Time Spent Without Symptoms of disease and Toxicity of Treatment (Q-TWiST).Design: A parallel observational comparative study.Methods: Patients with CEAP C-6,C-s RVU, assessed by duplex ultrasonography, were managed with either TWO2 (n = 46) or conventional compression dressings (CCD) (n = 37) for 12 weeks or till full heating. Patients were followed up at 3 monthly intervals.Results: At 12 weeks, 80% of TWO2 managed ulcers were completely heated, compared to 35% of CCD ulcers (p < 0.0001). Median time to full heating was 45 days in TWO2 patients and 182 days in CCD patients (p < 0.0001). The pain score threshold in TWO2 managed patients improved from 8 to 3 by 13 days. After 12-month follow-up, 5 of the 13 heated CCD ulcers showed signs of recurrence compared to none of the 37 TWO2 heated ulcers. TWO2 patients experienced a significantly improved Q-TWiST.Conclusion: TWO2 reduces recurrence rates, alleviates pain and improves the Q-TWiST. We believe it is a valuable tool. in the armamentarium of management of RVU. (C) 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.