Purpose/Objective(s): Describe the incidence and identify risk factors for seroma development following MBT. Materials/Methods: MBT patient data were prospectively recorded into a quality assurance database. Departmental and electronic records were reviewed to extract patient-, treatment-, and outcome-specific data. Stepwise logistic regression analysis was performed to identify factors predictive of development of any seroma including the subset of clinically significant seromas (CSS; defined as requiring multiple aspirations, biopsy, and/or excision). Variables analyzed included age, weight, history of diabetes, tobacco use, number of excisions, time from resection to catheter placement, placement technique and approach, catheter dwell time, overlying skin thickness, balloon volume, number of dwell positions, dosimetric factors (V100%, V150%, V200%), chemotherapy, hormone therapy, and post-brachytherapy infection. Results: MBT was performed in 109 patients, of whom 97 had minimum 6 months (median 36) post-MBT follow-up or earlier development of seroma. All patients received 34 Gy to 1cm depth from balloon edge, delivered twice daily in 10 fractions. Seroma developed in 41% of patients at a median of 3 months (range 0.1-25) post-MBT. One third of seromas (13% of all patients) developed CSS. The only factor identified as statistically significant for development of any seroma was catheter placement on day of resection versus >1 day later (59% vs 33%; p=0.0066). Post-MBT infection was highly statistically significant for development of CSS (64% vs 7%; p<0.0001). Prophylactic antibiotics reduced the risk of post-MBT infection from 37.5% to 6% (p=0.011). Conclusions: The incidence of CSS development after MBT is low. Post-MBT infection is a statistically significant predictor for CSS. The incidence of infection is reduced with prophylactic antibiotics.