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Piglet castration results in acute pain and stress to the animal. There is a critical need for effective on-farm methods of pain mitigation. Local anaesthesia using Tri-Solfen^® (Animal Ethics Pty Ltd., Melbourne, Australia), a topical local anaesthetic and antiseptic formulation instilled to the wound during surgery, is a newly evolving on-farm method to mitigate castration pain. To investigate the efficacy of Tri-Solfen^®, instilled to the wound during the procedure, to alleviate subsequent castration-related pain in neonatal piglets, we performed a large, negatively controlled, randomised field trial in two commercial pig farms in Europe. Piglets (173) were enrolled and randomised to undergo castration with or without Tri-Solfen^®, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Efficacy was investigated by measuring pain-induced motor and vocal responses during the subsequent procedure and post-operative pain-related behaviour in treated versus untreated piglets. There was a significant reduction in nociceptive motor and vocal response during castration and in the post-operative pain-related behaviour response in Tri-Solfen^®-treated compared to untreated piglets, in the first 30 min following castration. Although not addressing pain of skin incision, Tri-Solfen^® is effective to mitigate subsequent acute castration-related pain in piglets under commercial production conditions.