ObjectivesInfective endocarditis (IE) is a devastating disease with a 50% 1-year mortality rate. In recent years, medical authorities across the globe advised stricter criteria for antibiotic prophylaxis in patients with high risk of IE undergoing dental procedures. Whether such recommendations may increase the risk of IE in at-risk patients must be investigated.DesignProspectively registered systematic review and meta-analysis.Data sourcesMedline, Embase, Scopus and ClinicalTrials.gov were searched through 23 May 2022, together with an updated search on 5 August 2023.Eligibility criteriaAll primary studies reporting IE within 3 months of dental procedures in adults >18 years of age were included, while conference abstracts, reviews, case reports and case series involving fewer than 10 cases were excluded.Data extraction and synthesisAll studies were assessed by two reviewers independently, and any discrepancies were further resolved through a third researcher.ResultsOf the 3771 articles screened, 38 observational studies fit the inclusion criteria and were included in the study for subsequent analysis. Overall, 11% (95% CI 0.08 to 0.16, I2=100%) of IE are associated with recent dental procedures.Streptococcus viridansaccounted for 69% (95% CI 0.46 to 0.85) of IE in patients who had undergone recent dental procedures, compared with only 21% (95% CI 0.17 to 0.26) in controls (p=0.003). None of the high-risk patients developed IE across all studies where 100% of the patients were treated with prophylactic antibiotics, and IE patients are 12% more likely to have undergone recent dental manipulation compared with matched controls (95% CI 1.00 to 1.26, p=0.048).ConclusionsAlthough there is a lack of randomised control trials due to logistic difficulties in the literature on this topic, antibiotic prophylaxis are likely of benefit in reducing the incidence of IE in high-risk patients after dental procedures. Further well-designed high-quality case-control studies are required.Trial registration numberCRD42022326664.