Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/RpGDU5808CA Introduction: Foot-and-mouth disease (FMD) causes negative impacts on global food security, the livestock trade, national economies, and farming-family livelihoods, particularly in resourcepoor developing countries with inadequate biosecurity and low levels of vaccination from inadequate veterinary services. As smallholder farmers have limited understanding of diseaserisk management, their focus in FMD outbreaks is on accessing clinically effective therapies. However, most are provided inappropriate traditional treatments and/or topical or parenteral antibiotics, often delivered by paraveterinarians inadequately trained in antimicrobial custodianship. This results in negative financial impacts on livelihoods plus risks of food safety and development of antimicrobial resistance. We report the use of a novel pain-relief therapy for FMD. Methods: Clinical examinations in an outbreak of suspected FMD in April 2019 in Muang Khay village in Luang Prabang province, Laos confirmed signs and lesions of severe, subacute, ulcerative glossitis and interdigital dermatitis, typical of FMD. All affected buffalo (n=99) and cattle (n=37) presented for treatment in a population of 238 large ruminants, from 15 of 136 households, were administered a topical anesthetic pain-relief product (PRP) wound gel by spray-on (10-30 mL per animal) formulation developed for aversive husbandry procedures (Tri-Solfen, Animal Ethics, Australia). Results: Treatment with PRP resulted in immediate improvement in demeanor and locomotion, and no adverse events were observed. On follow-up interview, all owners confirmed that their animals were eating within 2 days and lesions had healed within 5 days. Having experienced the positive clinical impacts of PRP on affected animals, these and surrounding farmers were keen to purchase the PRP for future use. The veterinary authorities rapidly registered the PRP for FMD therapy in Laos due to the observed efficacy. Discussion: These findings suggest a potential paradigm shift from treating FMD with expensive antimicrobials, which risks antimicrobial resistance, to a new, less expensive therapeutic approach that reduces animal suffering and may motivate farmers to report disease to access treatment. Use of the PRP is suggested as an innovation that may improve future FMD management, particularly in developing countries.