Purpose: The aim of this systematic review was to estimate if an antibiotic prophylaxis regimen reduces implant failure and postoperative infection in healthy patients who are going to receive dental implants. Materials and Methods: An electronic database search (MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library) until June 30, 2019, for randomized controlled trials (RCTs) was performed. The Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias in individual studies was used. Patient- and implant-level data were extracted for the analyzed outcomes. The risk ratio (RR) and the 95% confidence interval were calculated as meta-analytic effects. A fixed- or a random-effect model was employed on the basis of the presence/absence of heterogeneity (I2 > 50%). Differences between groups were analyzed using the inverse of variance test. The Higgins Index and chi-square test were used to assess the studies' heterogeneity. Additionally, in order to evaluate the power of evidence and to adjust the meta-analytic findings for type 1 and 2 errors, a trial sequential analysis (TSA) was performed. Results: Nine studies including 1,984 patients and 3,588 implants were selected. Eight hundred eighty-five patients (1,617 implants) received no antibiotics or a placebo therapy before the implant surgery; 1,971 implants (1,099 patients) were treated with an antibiotic therapy. The meta-analysis at the patient level showed a statistically significant reduction in the rate of early implant failure associated with the use of antibiotics (I2 = 0%) (RR = 0.32 [0.20, 0.51], P > .001). Similar results were obtained after pooling the implantlevel data with the fixed-effect model (RR = 0.33 [0.22, 0.51], P > .001). Such results were also confirmed by the TSA after adjusting for type 1 and 2 errors. Conclusion: The results of this systematic review with meta-analysis indicate that an antibiotic prophylaxis prevents early implant failures in the case of healthy patients. No information can be provided on peri-implant infections. Keywords: antibiotics, chemotherapy, epidemiology, meta-analysis, prophylaxis, review (systematic)