Background: Central venous catheters (CVCs) play an important role during cardiac surgery. Topical tissue adhesives form a thin film of coating that becomes bound to the keratin in the epidermis. The advantage of this “super glue” lies in its antimicrobacterial activity. This study aimed to evaluate fixation of CVCs with topical tissue adhesive in patients (prone to bleed) undergoing cardiac surgery, regarding its ability to reduce the incidence of pericatheter leakage.Methods: This randomized controlled trial included 150 patients >15 years of age who were (1) scheduled to undergo elective cardiac surgery, (2) required CVC insertion at the internal jugular vein, and (3) were scheduled for transfer postoperatively to the cardiac intensive care unit. We randomly assigned patients to a topical tissue adhesive group (TA) or a standard control group (SC). The primary outcome was a change of dressing immediately postoperatively due to pericatheter blood oozing. Secondary outcomes were the number of dressings, total dressings per catheter-day, and composite outcome of catheter failure within 3 days. Both intention-to-treat and per-protocol analyses were performed. Seven patients violated the protocol (three TA patients, and four SC patients).Results: Regarding the primary outcome, the SC group had a significantly higher incidence of dressing change immediately postoperatively due to pericatheter leakage than the TA group in both the intention-to-treat analysis (5.33% vs 18.67%, RR 0.25 [95%CI 0.08 to 0.79], P = 0.012) and the per-protocol analysis (5.56% vs 16.90%, RR 0.289 [95%CI 0.09 to 0.95], P = 0.031). There were no significant differences between the two groups for the number of dressings, total dressings per catheter-day, or composite outcome of catheter failure within 3 days. Multiple logistic regression analysis was performed to adjust baseline characteristics which were different in the per-protocol analysis. The result showed that the risk ratios of immediate postoperative dressing change in TA patients were 0.25 compared to the SC group ([95%CI 0.07 to 0.87], P = 0.029) in the per-protocol analysis.Conclusion: Use of a topical tissue adhesive can reduce the incidence of immediate postoperative pericatheter blood oozing.Trial registration: TCTR20180608004, retrospectively registered on June 06, 2018. http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=3610