Traditional skin sutures (TSS) and metal skin clips (SC) are the most common devices utilized for closure of surgical incisions. They are safe and effective, although they require instruments to apply them, are time consuming and, above all, create an extra staff and cost burden for removal of sutures/staples. The ideal incision closure should be simple, effective, safe, rapid, inexpensive, painless, cosmetic and bactericidal. The present study was designed to determine the safety and efficacy of N-butyl octyl cyanoacrylate (NCA) tissue adhesive, a liquid bandage surgical product, for wound closure in brain surgery. Our prospective randomized controlled study compared NCA with traditional methods for wound closure in brain surgery. Over a 6-month period, 40 patients who underwent a supratentorial elective craniotomy were enrolled and randomly allocated into two groups. The 20 participants in group A were treated using a new NCA tissue adhesive while the 20 participants in group B were treated using either nylon monofilament, TSS or SC. In the post-operative period and during follow-up, two different nurses (the second nurse was blinded to the closure method used) recorded details regarding wound aspects, complications and patient satisfaction using a modified version of the Hollander Wound Score Scale. We found no difference in the cosmetic outcome of the two groups, or in wound complications rate, but the patient satisfaction score was higher in group A (9.4 vs. 7.1; p<0.005). The mean application time of the tissue adhesive was significantly faster than that of the standard suture (115s vs. 300s; p<0.001); in the skin clips subgroup it was 105s. Our study suggests that the new NCA tissue adhesive is a safe, effective and reliable skin closure for neurosurgical procedures in the supratentorial region; it also achieves optimal cosmetic results, is less time consuming to use and has greater patient satisfaction. However, further studies with a larger number of patients are necessary to corroborate these results.