Background <p>Knotless barbed suture is a novel suture device that has barbs placed along the entire suture length to aid in engaging the suture material into the tissues while suturing and obviating the need for knots to secure the sutures. So, the current study aims to assess knotless sutures’ effectiveness over conventional sutures in terms of wound closure following mandibular impacted third molar (MI3M) surgery.</p> Methods <p>A controlled randomized prospective study on 40 subjects having at least one asymptomatic MI3M was performed. Subjects were randomized and distributed in two independent groups using a sealed impervious envelope. The groups were named as Group K (study group), and Group V (control group). The primary outcome variable measured were trismus, edema and pain post-operatively whereas the secondary outcome variable measured were suturing time, wound healing and post-operative quality of life after MI3M surgery.</p> Results <p>The results of the current study showed that the intensity of post-operative pain, edema and trismus when measured on day 2 and day 7 showed significant difference (p ˂ 0.05) in the study group. Also, the duration of suturing was less and post-operative quality of life was improved in the knotless suture group than the control group.</p> Conclusion <p>Knotless sutures is a safe, effective and novel method of suturing in terms of closure of wound following MI3M that can be practiced on regular basis. Its efficacy in other fields needs to be evaluated with a greater sample size in further studies.</p> Clinical Trial Registration Number <p>CTRI/2021/02/031092 [Registered on: 08/02/2021].</p>