Abstract Background According to the current guidelines of the European Society of Cardiology, patients with left-sided infective endocarditis are treated with intravenous antibiotics for 4–6 weeks, leading to extensive hospital stay and high costs. Recently, the Partial Oral Treatment of Endocarditis (POET) trial suggested that partial oral treatment is effective and safe in selected patients. Here, we investigated if such patients are seen in our daily clinical practice. Methods We enrolled 119 adult patients diagnosed with left-sided infective endocarditis in a retrospective, observational study. We identified those that would be eligible for switching to partial oral antibiotic treatment as defined in the POET trial (e.g. stable clinical condition without signs of infection). Secondary objectives were to provide insight into the time until each patient was eligible for partial oral treatment, and to determine parameters of longer hospital stay and/or need for extended intravenous antibiotic treatment. Results Applying the POET selection criteria, the condition of 38 patients (32%) was stable enough to switch them to partial oral treatment, of which 18 (47.3%), 8 (21.1%), 9 (23.7%) and 3 patients (7.9%) were eligible for switching after 10, 14, 21 days or 28 days of intravenous treatment, respectively. Conclusion One-third of patients who presented with left-sided endocarditis in routine clinical practice were possible candidates for switching to partial oral treatment. This could have major implications for both the patient’s quality of life and healthcare costs. These results offer an interesting perspective for implementation of such a strategy, which should be accompanied by a prospective cost-effectiveness analysis.