Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.