Purpose <p>Epidemiological and microbiological characteristics of endogenous endophthalmitis (EE) can vary by population and geographical area, with different risk factors. This study from a tertiary care centre aimed to provide additional data from one European country in the field of EE.</p> Methods <p>This retrospective study was conducted on patients diagnosed with EE at the University Hospital of Grenoble-Alpes, France, between 2014 and 2023. General and ocular clinical data, along with microbiological findings, were collected at baseline and on follow-up.</p> Results <p>Thirty-three patients were diagnosed with EE in this study with a mean age of 70 ± 17.7 years, and 51.5% were male. Most cases were unilateral. Common health conditions included cancer, and diabetes mellitus, with endocarditis being the leading source of infection. Baseline visual acuity ranged from 20/20 to no light perception. Blood cultures were positive in 87.8% of the cases. Gram-positive bacteria, especially <i>Staphylococcus aureus</i>, were the most common pathogens, followed by <i>Candida albicans</i>. Pars plana vitrectomy was performed in 33% of the patients. At the end of the follow-up, four patients had lost vision, two developed phthisis, and mortality was reported in 24% of the patients.</p> Conclusion <p>This study on endogenous endophthalmitis highlights that, in Europe, the primary risk factors are cancer and diabetes, with endocarditis being the most common source of infection. According to our findings, Gram-positive bacteria, particularly <i>Streptococcus</i> species and <i>Staphylococcus aureus</i>, are the most frequently identified pathogens in Europe. These findings differ significantly from reports originating from the USA and Asia.</p>