OBJECTIVES: Although controversy exists regarding the efficacy of antibiotic prophylaxis for patients at risk of infective endocarditis, expert committees continue to publish recommendations for antibiotic prophylaxis regimens. This study aimed to evaluate the efficacy of four antimicrobial regimens for the prevention of bacteraemia following dental extractions. METHODS: The study population included 266 adults requiring dental extractions who were randomly assigned to the following five groups: control (no prophylaxis); 1000/200 mg of amoxicillin/clavulanate intravenously; 2 g of amoxicillin by mouth; 600 mg of clindamycin by mouth; and 600 mg of azithromycin by mouth. Venous blood samples were collected from each patient at baseline and at 30 s, 15 min and 1 h after dental extractions. Samples were inoculated into BACTEC Plus culture bottles and processed in the BACTEC 9240. Conventional microbiological techniques were used for subcultures and further identification of the isolated bacteria. The trial was registered at ClinicalTrials.gov with ID number NCT02115776. RESULTS: The incidence of bacteraemia in the control, amoxicillin/clavulanate, amoxicillin, clindamycin and azithromycin groups was: 96%, 0%, 50%, 87% and 81%, respectively, at 30 s; 65%, 0%, 10%, 65% and 49% at 15 min; and 18%, 0%, 4%, 19% and 18% at 1 h. Streptococci were the most frequently identified bacteria. The percentage of positive blood cultures at 30 s post-extraction was lower in the amoxicillin/clavulanate group than in the amoxicillin group (P < 0.001). The incidence of bacteraemia in the clindamycin group was similar to that in the control group. CONCLUSIONS: Bacteraemia following dental extractions was undetectable with amoxicillin/clavulanate prophylaxis. Alternative antimicrobial regimens should be sought for patients allergic to the β-lactams.