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Background/Aim: Using drains after breast surgery is a preventive, but invasive measure to reduce seroma formation. A polyurethane-based tissue adhesive (TissuGlu®) might facilitate drainage-free wound healing after mastectomy in a non-invasive manner. Patients and Methods: Retrospectively, data from 84 patients (42 receiving TissuGlu®, 42 receiving a drainage) who underwent mastectomy, were collected (90 days postoperative follow-up). Study endpoints were defined as the number of fluid-related postoperative clinical interventions, cumulative volume of postoperative wound fluid, duration of hospitalization and postoperative complications. Results: In the entirety of postoperative interventions, no significant difference could be demonstrated (p=0.298). The drainage arm showed significantly less seroma aspirations (p=0.024) and complications (p=0.012). A significantly reduced length of hospitalization (p<0.001) and less cumulative wound secretion volume (p<0.001) appeared in the TissuGlu® group. Conclusion: The polyurethane-based tissue adhesive is a less invasive alternative to drain use in mastectomy.