BACKGROUND The self-assembling peptide barrier T45K (SAPB-T45K) is an oligopeptide that rapidly forms a biocompatible hemostatic barrier when applied to wounds.OBJECTIVE Evaluate safety and performance of SAPB-T45K in cutaneous surgery.MATERIALS AND METHODS In this single-blind study, after sequential shave excision of 2 lesions, wounds were randomized (intrapatient) to SAPB-T45K or control treatment. Safety was assessed at treatment, Day 7, and Day 30. Performance was evaluated using time to hemostasis (TTH) and ASEPSIS wound scores, with a subgroup analysis for patients with or without antiplatelet therapy.RESULTS Each of 46 patients (10 [22%] with antiplatelet therapy) received randomized SAPB-T45K or control treatment for 2 wounds. Safety assessments were similar, and ASEPSIS scores reflected normal healing in both wound groups. SAPB-T45K demonstrated significantly faster median TTH (24.5 [range, 7-165] seconds) compared with control (44 [10-387] seconds), for a 41% median TTH reduction (18 [95% confidence interval, 7-35] seconds, p < .001). SAPB-T45K provided an identical median TTH of 24 seconds, regardless of antiplatelet therapy. Control median TTH was 90 and 40 seconds for patients taking or not taking antiplatelet therapy, respectively.CONCLUSIONS SAPB-T45K provided significantly faster median TTH versus control, especially with antiplatelet therapy, and safety profiles were similar.