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Objective: To document the efficacy of a combined therapeutic strategy in achieving rapid wound healing in patients with long-standing ulcers., Materials and Methods: Outpatients with hard-to-heal venous leg ulcers were included in an interventional, prospective, single-arm, mono-centre study and treated with autologous punch grafting, TLC-NOSF dressing and multi-type compression therapy. The primary outcome was the percentage of healed wounds by week 12. Secondary outcomes included time-to-reach wound closure, wound area reduction, treatment acceptability and safety., Results: From November 2018 to October 2019, 42 patients with 51 ulcers were included (23 males, 70.6±40.8 years old, with multiple comorbidities). Despite poor wound healing prognosis at baseline (47% of recurrent ulcers, with a mean duration of 15 months and a mean area of 12.6cm 2 ), wound healing was achieved in 47 ulcers (92%) after a mean period of treatment of 25±13 days. A relative wound area reduction>75% was also reached in three additional ulcers by the last evaluation visit. No adverse event related to the procedure was reported throughout the study period. The associated treatment were very well tolerated and accepted by the patients., Conclusions: The evaluated procedure induced fast re-epithelisation of the treated ulcers. Based on our experience, this simple and successful reparative strategy may be considered as an interesting option in the treatment of venous leg ulcers of poor prognosis., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)