Introduction: Seroma formation is a serious postoperative complication. Since the management algorithms available in the literature are scarce, we aimed to analyze our experience with postoperative seroma in order to identify indicators for revisional surgery and propose recommendations for management. Methods: This retrospective study included all patients with postoperative seroma treated in a tertiary university hospital from 2008 to 2020. Patients’ demographics, medical history, and seroma treatment details were recorded and analyzed. Results: Overall, 156 patients were included: 41% were initially treated through needle aspiration, with 61% eventually undergoing surgical treatment for postoperative seroma. Comorbidities, such as heart failure and coronary heart disease, were significantly associated with an increased need for revisional surgery (p < 0.05). Both a duration of >40 days of repeated needle aspirations and drain re-insertions were significantly correlated with an increased risk for revisional surgery (p < 0.05). Conclusion: Patients requiring seroma aspiration should be counseled on surgical treatment sooner rather than later, as prolonged aspiration time (over 40 days) greatly increases the risk of surgical revision. Moreover, the reinsertion of a drain should only be used as a temporizing measure, at most, and patients requiring a drain to control the size of the seroma should promptly be scheduled for a surgical revision.