Aim: The present study was conducted with the aim of evaluating the effectiveness of antimicrobial therapy following extraction of an impacted mandibular third molar. Materials and methods: This randomized controlled trial was conducted on a total of 60 patients who were randomly assigned into three groups: Group I individuals were given 625 mg of combined amoxicillin and clavulanic acid tablet; 625 mg of combined amoxicillin and clavulanic acid tablet + 400 mg metronidazole tablet was given to group II individuals; whereas group III individuals were assigned no treatment. All the individuals underwent surgical extraction of impacted mandibular third molars under strict aseptic techniques, with minimal trauma to the surrounding tissues. Mouth opening in millimeters was recorded postoperatively using Vernier calipers on the 1st, 3rd, 5th, and 7th days. A 4-point visual analog scale (VAS) was used for assessing postoperative pain. Patient satisfaction was further assessed in a subjective manner using a graded scale from “very satisfied” to “very unsatisfied”. Results: The present study included individuals between the ages of 20 and 35 years. Group II individuals showed slightly better satisfaction than the other group individuals. There was no statistically significant difference between the mean age of groups. It was observed that on day 3, the number of individuals with severe pain was slightly reduced in the group I compared with group III individuals. On day 5, participants with no pain were significantly more in group II followed by group I. Furthermore, there was a statistically significant difference between the study groups with respect to mouth opening on days 3 and 5. Conclusion: It was concluded from this trial that the administration of postoperative antimicrobials showed no significant differences in the degree of postoperative complications that occur following the surgical extraction of impacted mandibular third molars. Clinical significance: Antimicrobial drugs are routinely used to reduce the chances of surgical site infection, either preoperatively or postoperatively. Therefore, the clinicians should have sound knowledge about choosing the better antimicrobial drug after the extraction of impacted third molars.