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Pain in chronic venous ulcers (CVUs) notably increases with the usual cleaning of the wound. Chronic pain is usually poorly controlled even with the multiple analgesic treatments available. Analgesics can have different serious adverse effects and medical interactions in old patients with several comorbidities. This study reports the efficacy and safety of topical sevoflurane for treatment of pain in CVUs.We report a descriptive and retrospective study of 30 patients older than 65 years with painful CVUs refractory to conventional analgesic treatments. Patients received topical sevoflurane treatment before the usual cleaning of the ulcer. Cleaning visits with sevoflurane every 2 days for a period of 1 month were scheduled. We compared the visual analog scale results and analgesic drugs for cleaning with and without topical sevoflurane. The systemic pharmacokinetics of sevoflurane after topical application has not been determined.Pain related to CVUs decreased with topical sevoflurane. Sevoflurane had an analgesic effect with latency time between 2 and 7 minutes. The duration of analgesia ranged between 8 and 18 hours. The time needed to take an analgesic treatment increased after application of sevoflurane. The use of other conventional analgesic drugs, including paracetamol, metamizole, nonsteroidal anti-inflammatory drugs, tramadol, and major opioids, was progressively reduced. The main local adverse effects were mild and transient, including heat, pruritus, and erythema. There were no systemic adverse effects.Topical sevoflurane has an intense, fast, and long-lasting local analgesic effect with an adequate safety profile. It also diminishes the taking of other conventional analgesic drugs. Topical sevoflurane is an efficient and safe therapeutic alternative for refractory painful CVUs.