BACKGROUND The aim of this study was to describe a single unit experience for the treatment of acute infective endocarditis, for patients older than 75 years and to analyse the results of early surgery. PATIENTS AND METHODS From January 1991 to June 2006 348 consecutive patients with definite acute infective endocarditis, according to Duke criteria, were prospectively enrolled in our database. Among these, 75 patients older than 75 years (mean age 79.8+/-4 years) were analysed and compared to 273 younger patients. RESULTS The patients older than 75 years (group A, 75 patients) had a more severe clinical status than the younger patients (group B, 273 patients) with a comorbidity index amounting to 4.9+/-1.8 and 2.9+/-1.0 respectively (p=0.0001). Patients were treated medically (group A 53 pts vs group B 124 pts) or surgically (group A 22 pts vs group B 149 pts) (p=0.001). The in-hospital mortality rate for group A and B was comparable (16% vs 19%; p=0.3). Multivariate analysis identified for patients older than 75 years, severe sepsis (p=0.001, OR=12, CI [6-24]), and major neurological events (p=0.02, OR=3, CI [1.1-7.5]) as the two factors related to higher in-hospital mortality and surgery (p=0.006, OR=0.4, CI [0.2-0.7]) as the factor related to a lower in-hospital mortality. The overall survival of the older group at 36 months was 40.8+/-6.8%. Multivariate analysis for older patients identified comorbidity index (p=0.001) (HR 1.1, CI [1-1.2]), severe sepsis (p=0.0001) (HR 3.3, CI [2.2-5.2]), valvular prosthesis (p=0.0002) (HR 2.4, CI [1.5-4]) and major neurological event (p=0.04) (HR 1.7, CI [1-3]) as factors related to overall mortality and surgery (p=0.001) (HR 0.4, CI [0.3-0.6]) as a factor related to a better overall survival. CONCLUSION The immediate results of treatment for endocarditis are comparable between elderly and younger patients. The long-term prognosis for the elderly patients is worse, mainly related to a higher comorbidity index. Surgery in elderly patients may be a reasonable option, and should be considered in selected elderly patients.