Aim: The present study was undertaken to compare the efficacy of isoamyl 2-cyanoacrylate tissue adhesive with 3-0 vicryl rapide suture for wound closure after the removal of impacted mandibular third molar. Materials and methods: In this prospective study done in 2018–2020, sample consisted of 60 patients with unilateral impactions divided in two groups equally. In group I, wound closure was done with tissue adhesive and in group II with 3-0 vicryl rapide suture. Patients were evaluated for pain, swelling and trismus preoperatively, immediate postoperatively, postoperative day 2 and 7. Bleeding was assessed immediate postoperatively, postoperative day 2 and 7. Healing was assessed on postoperative day 2 and 7. Observations: Statistically significant difference was observed in terms of pain on postoperative day 2 and 7 between both the groups (p value—0.028^* and 0.002^*). In the immediate postoperative period, there was statistically highly significant difference in bleeding between the two groups (p value—0.000^**). Statistically significant difference was also observed in terms of wound healing on postoperative day 2 and 7 (p value—0.011^* and 0.024^* respectively). Statistically significant difference was observed for time of closure and total number of rescue analgesic taken between two groups (p value—0.000^** and 0.000^**, respectively). Conclusion: This study concluded that vicryl rapide suture is an optimal alternative for wound closure after removal of impacted mandibular third molar as compared to tissue adhesive.