Endophthalmitis due to Listeria monocytogenes is an exceedingly rare cause of listeriosis. Here, we report two cases which occurred in patients with different medical history, a 46-years-old immunocompetent woman and an elderly man with several comorbidities. There was no history of trauma or surgery in either patient suggesting an endogenous origin. Despite antibiotic treatment, both patients showed poor visual acuity outcomes. Subtyping clinical isolates using whole genome sequencing could allow to identified Listeria monocytogenes strains involved in rare clinical manifestation, such as in unusual anatomical sites, even in immunocompetent patients, and could be helpful in the redefinition of the hypervirulent strains.