Introduction: The popular wound closure methods for carpal tunnel decompression (CTD) include non-absorbable and absorbable sutures which have comparable results in clinical outcomes. However, these wound closure methods are recommended to keep a wound dry which may limit some ADLs. We conducted a prospective randomized controlled trial that compares clinical outcomes and costeffectiveness in a skin closure following CTD between absorbable sutures plus a 2-octyl cyanoacrylate tissue adhesive (2OCA) versus non-absorbable skin sutures plus a waterproof dressing (NSPWD). Materials and methods: We enrolled 120 patients undergoing CTD into two groups: 2OCA and NSPWD, with 60 patients in each group. Number of dressing changes, Quick DASH, pain VAS, cosmetic VAS, patient satisfaction VAS, and Hollander wound evaluation score, costeffectiveness, and post-operative complications were collected at pre-operative period and two and six weeks postoperatively. Results: Slightly better patient satisfaction VAS (7.9 vs 7.2, p=0.018) and cosmetic VAS (8.0 vs 7.2, p=0.025) were observed in 2OCA at 2 weeks. Meanwhile, NSPWD revealed lesser times of dressing change (Median, mode, IQR: 0/0/0 vs 2/3/2, p<0.001). The total wound-related costs include dressing change and suture removal cost ($15.9 for 2OCA vs $19.2 for NSPWD, p=0.002) although an initial woundrelated cost in 2OCA was higher ($15.7/case vs $7.9/case, p<0.001). Conclusions: Our study revealed that the supplementary tissue adhesive to absorbable sutures following CTD could reduce total wound-related costs while clinical outcomes might not be considered clinically significant.