Several anaesthetic drugs have demonstrated antibacterial properties in vitro. Anaesthetics can primarily affect the cell wall of both susceptible and multi-resistant bacteria. They may also have a synergistic effect with conventional antibiotics through an unknown mechanism. We present three cases of a chronic venous ulcer infected by multi-resistant bacteria refractory to conventional systemic antibiotics, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Treatment with topical sevoflurane was performed for 1 month without systemic antibiotics. Patients with an MRSA infection showed progressive improvement with negative culture at the end of the treatment. Multi-drug-resistant P. aeruginosa infection persisted at the end of treatment with positive culture. The local adverse events were mild and transient, including heat, pruritus and erythema. Topical sevoflurane may have an antibacterial effect on sensitive and multi-resistant strains. It can allow more complete surgical cleaning, leaving a cleaner wound with less fibrin and necrotic tissue. This decreases the bacterial colonisation and therefore the infectious risk, the bad smell and the exudation. The simultaneous use of conventional antibiotics and topical sevoflurane can have a synergistic antimicrobial effect.