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Background: Lipomas are common benign tumors of mesenchymal origin that are composed of mature adipocytes. Giant lipomas have a diameter ≥ 10 cm in one or more dimensions or weigh at least 1,000 g. The surgical excision of a giant lipoma requires extensive dissection, increasing the risk of a seroma, which can cause surgical site complications such as wound infection and necrosis. Sclerotherapy with Abnobaviscum (<i>Viscum album</i> extract) is a relatively new technique used to reduce malignant pleural effusion. In this study, we evaluated the effectiveness of prophylactic sclerotherapy using Abnobaviscum to decrease seroma after giant lipoma excision.Methods: We conducted a retrospective medical record review of patients who underwent surgical excision for giant lipoma of the neck from January 2019 to December 2022. Sclerotherapy was performed on the first postoperative day in patients who consented to the procedure, and Abnobaviscum was instilled through the existing Hemovac drain. We compared the clinical course between those who underwent postoperative sclerotherapy and those who did not.Results: Among the 30 patients who underwent giant lipoma excision, we applied sclerotherapy with Abnobaviscum to 15 patients. The average time from surgery to Hemovac removal was statistically shorter in patients who underwent sclerotherapy (<i>p</i>= 0.004). Furthermore, seroma formation was significantly reduced in patients receiving sclerotherapy (<i>p</i>= 0.003).Conclusion: In patients undergoing giant lipoma excision, sclerotherapy using Abnobaviscum helps reduce postoperative seroma formation during the initial postoperative period. It can be an excellent method to reduce complications related to seroma and attenuate patients’ postoperative burden.Abbreviations: BMI, body mass index; DM, diabetes mellitus; HTN, hypertension; NSAIDs, nonsteroidal anti-inflammatory drugs; POD, postoperative day