The POET trial demonstrated that moving from intravenous to oral antibiotics in stable patients with left-sided infective endocarditis (IE) was noninferior to fully parenteral treatment. However, it did not compare outpatient strategies.The OraPAT-IE GAMES trial is a noninferiority, multicenter, randomized, open-label study aimed to compare partial oral versus outpatient parenteral antibiotic therapy (OPAT) for consolidation of antibiotic treatment in left-sided IE. A total of 342 stable patients with IE caused by selected micro-organisms will eventually be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or OPAT. The primary end-point is a composite of all-cause mortality, unplanned cardiac surgery, relapse of positive blood cultures and/or unplanned hospital admission. Patients are followed-up for 6 months after completing antibiotic therapy.This trial seeks to demonstrate the equivalent efficacy of the two outpatient strategies currently available for stable patients with IE in the consolidation phase of antibiotic treatment.In a global context of limited healthcare resources and a sustained increase in elderly and frail patients, it is of great importance to demonstrate the effectiveness and safety of outpatient management strategies that could reduce the duration of conventional hospitalizations with their potential complications and inherent costs.EudraCT: 2020-001024-34.gov identifier: NCT05398679.