Objective: This study was conducted to compare the anesthetic and analgesic efficacy of bupivacaine with other local anesthetic agents routinely used for mandibular third molar surgery. Method and materials: Four electronic databases (PubMed, Scopus, Cochrane, and Web of Science) were explored to isolate randomized controlled trials up to 10 February 2019. The anesthetic and analgesic efficacies were assessed using six evaluation outcomes: onset of anesthesia, success of anesthesia, duration of anesthesia, duration of analgesia, pain score on the fourth postoperative hour, and number of analgesics consumed. Stata software (version 13, StataCorp) was used to analyze the data. Results: Fourteen studies met the specified criteria. The sample consisted of 1,078 mandibular third molar surgeries performed in 858 patients. Bupivacaine, lidocaine/lignocaine, articaine, etidocaine, levobupivacaine, and carbonated bupivacaine were the local anesthetics used. Compared with other anesthetic agents, bupivacaine showed longer duration of anesthesia (weighted mean difference [WMD] 123.431 minutes; 95% confidence interval [CI] 34.01 to 212.851; P = .007), lower pain score at the fourth and eighth postoperative hours (4 hr-WMD 2.757; 95% CI 0.893 to 4.62; P = .004; 8 hr-WMD 1.697; 95% CI 1.178 to 2.216; P .001), and lower number of analgesics requirement (WMD 0.663; 95% CI 0.258 to 1.067; P = .001). The onset of anesthesia was slower for bupivacaine (WMD 0.865 minutes; 95% CI 0.799 to 0.931; P .001). However, for success of anesthesia (risk ratio 1.003; 95% CI 0.972 to 1.035; P = .831) and duration of analgesia (WMD 45.285 minutes; 95% CI −48.021 to 138.537; P = .342), the local anesthetic agents showed no significant differences. Conclusions: Except for the onset of anesthesia, bupivacaine showed better anesthetic and analgesic properties than other local anesthetic agents for mandibular third molar surgery. Keywords: bupivacaine, local anesthesia, mandibular third molar surgery, systematic review