•ETN is suggested as an infectious disease, not related to viruses.•Intradermal inoculation triggers the initial lesions characteristic of ETN and resulted in partial loss of pinnae cartilage.•The full aetiology, particularly related to progression, remains unclear. Swine ear-tip necrosis (ETN) is a disease of global presence and unclear aetiology. Little evidence is available regarding the nature of this disease. The aim of this work was to investigate if ETN is an infectious disease that could be replicated using a lesion macerate inoculum. A source farm with a history of ear-tip necrosis was identified and five weeks-old pigs (n = 12) from this farm were housed under controlled conditions and intradermally inoculated with ETN lesion macerates (right ear, n = 10) or sterile inoculum (left ear, n = 10). Two pigs were not inoculated, serving as sentinels. All animals were clinically monitored daily during 21 days, and a ETN ear score was used to follow disease progression. Anaerobic (n = 2) and aerobic (n = 2) overnight cultures, as well as raw aliquots of the lesion macerate inoculum (n = 2) and control inoculum (n = 2) were submitted for metagenomic sequencing. All inoculated ears developed lesions suggestive of early ETN, but none progressed to result in loss of the ear pinna. All completely resolved 21 days post-inoculation. Post-mortem investigation revealed areas of fibrosis, characterized by a granulomatous response in the inoculated ears (5/10) and in 1/10 control ears. Metagenomic analysis identified the presence of previously suggested bacterial etiological agents, but no relevant viral, fungal or protozoan agents in the inoculum. ETN etiology remains unclear, but an infectious cause and bacterial agents are suggested to be at least partially implicated in disease pathogenesis. Virus and fungi do not seem to significantly contribute to disease.