OBJECTIVES: Guidelines recommend penicillin, amoxicillin or ceftriaxone for the treatment of streptococcal infective endocarditis (IE) but do not specify the criteria for choosing the β-lactam to be used. Our objectives were to identify which antibiotics are preferentially considered for susceptibility testing and treatment. METHODS: A practice survey was addressed to infectious disease specialists and clinical microbiologists. The questionnaire was diffused to international learned societies as an online google form between September 2022 and 2023. RESULTS: 94 responses were collected, mainly from participants residing in Europe (60/94, 69%). Over 80% (72/88) of respondents reported that minimum inhibitory concentrations (MICs) other than that of penicillin G were routinely measured, including those of ceftriaxone (43/88, 49%), and ampicillin/amoxicillin (55/88, 63%). For treatment of penicillin-susceptible increased exposure isolates (MIC > 0.125 mg/L and ≤ 2 mg/L), the ß-lactams with the lowest MIC were the molecules of choice for 61% (51/83) of respondents. For penicillin-resistant isolates (MIC > 2 mg/L), non-ß-lactam antibiotics were the preferred molecules, followed by the lowest MIC ß-lactam (48%, 38/79, and 43%, 34/79, respectively). CONCLUSIONS: Despite disparities in antibiotic susceptibility testing, we observed a converging approach toward the treatment of choice for IE due to penicillin-non-susceptible isolates, favoring the lowest MIC β-lactam. Further studies are needed to determine the optimal antibiotic therapy for difficult-to-treat streptococcal IE in order to revise future guidelines.