Purpose <p>Advances in interstitial brachytherapy for brain cancers have revived interest in this treatment platform. However, the impact of this therapy on hospital quality measures remains poorly characterized. Here, we utilized the National Readmission Database (NRD) to address this gap in knowledge by identifying associations between interstitial brachytherapy and hospital course, discharge disposition, and readmission rates.</p> Methods <p>We identified patients in the United States of America with malignant brain tumors who had undergone either craniotomies (C) for tumor resection or craniotomies augmented with adjuvant interstitial brachytherapy (C + IB) in the National Readmission Database (NRD, 2010–2018). Propensity-score weighting and survey regression techniques were used for analysis.</p> Results <p>Over the study period, the number of craniotomies with adjuvant interstitial brachytherapy (C + IB) steadily decreased. For brain metastasis (BM) patients, C + IB and C patients exhibited comparable length of hospital stay (aIRR: 1.01, CI₉₅ 0.86–1.18, p = 0.918) and routine discharge to home or self-care (aOR:0.95, CI₉₅:0.61–1.50, p = 0.838). However, primary brain tumor (PBT) patients who underwent C + IB showed longer hospital stay (aIRR:1.43, CI₉₅:1.03–1.99, p = 0.032) and were less likely to undergo routine discharge (aOR: 0.38, CI₉₅:0.20–0.74, p = 0.005) relative to the C cohort. Despite these differences, C + IB and C patients showed comparable 30- or 90- day readmission risks. The profile of readmission diagnoses was also similar. Cost-analysis suggests that IB increased the median total charge by $19,184 (p = 0.003).</p> Conclusions <p>Our NRD analysis suggests that adjuvant interstitial brachytherapy did not alter hospital course/readmission risk for brain metastasis patients. However, primary brain tumor patients who underwent this therapy showed longer hospitalization and an increased likelihood of non-routine discharge.</p>