Despite rapid advancements in targeted therapeutics and increasingly conformal radiation techniques, limited data exist regarding reirradiation of primary brain tumors. Herein, we provide an initial report of our institutional experience with reirradiation of primary brain tumors, hypothesizing that reirradiation can be delivered safely in select patients with acceptable oncologic outcomes and toxicities.With IRB approval (828228), we retrospectively reviewed patients who received at least 2 courses of radiation for primary brain tumors at our institution between 2010-2020. Factors prompting study exclusion included: 1) diagnosis of brain metastases, 2) age < 18 years, and 3) follow-up < 2 months. Primary outcomes were intracranial progression free (PFS), and overall survival (OS). Secondary outcomes were acute toxicities, classified as ≤3 months from the start of radiation. Cohort characteristics were analyzed using descriptive statistics and survival estimates were generated using the Kaplan-Meier method.We identified 45 patients (Median (IQR) age-at-reirradiation, 46 (35-38) years; Men, N = 29; Women, N = 16) who met study inclusion criteria. Median follow-up was 7.6 (2.1-13.9) months. Gliomas were the most common diagnosis (N = 33), including 61% glioblastoma. Thirty-eight patients underwent initial surgical resection (GTR, 38%; STR, 47%). Median dose during the initial radiation course was 5940 Gy in 33 fractions. Median interval to reirradiation was 1.8 (0.8-3.1) years. Overall, 75% of patients received reirradiation with IMRT (median dose/fraction, 3500 cGy/10), while 25% patients received SRS (median dose/fraction, 2100 cGy/). Median intracranial PFS was 5.7 months and median OS was 9.6 months. Acute grade ≥3 toxicities occurred in 5 patients and included anorexia (N = 1), cognitive disturbance (N = 1), headache (N = 1), fatigue and aphasia (N = 1), and urinary incontinence (N = 1).In this single-institution series, reirradiation of primary brain tumors was safe and effective with acceptable clinical outcomes and low rates of severe acute toxicities. Additional data on dosimetric details and late toxicities are forthcoming.J. Wei: None. P. Santos: None. R.A. Lustig: None. G. Kurtz: None. J.F. Dorsey: None. J.E. Shabason: None. M. Alonso-Basanta: Travel Expenses; Varian, IBA.