Background: Hypofractionated stereotactic radiotherapy (SRT) has been increasingly used for brain metastases (BMs) from non-small cell lung cancer (NSCLC). However, the prognostic factors, pattern of failure and clinical utility of re-irradiation for these patients remain have not been fully understood. Methods: Metastatic NSCLC patients receiving SRT that covering all of the intracranial tumor lesions and without prior whole brain radiotherapy (WBRT) were retrospectively enrolled. Local recurrence free survival (LRFS), intracranial progression free survival (iPFS) and overall survival (OS) were calculated from the initiation of SRT. Post intracranial progression survival (OS2) was measured from the initial intracranial disease progression. Results: From 2018/07 to 2022/05, 218 patients were identified, with 142 (65.1%) having only one BM and 76 (34.9%) harboring 2-5 BMs. With a median follow-up of 31.1 (range, 1.0-44.6) months, median LRFS, iPFS and OS was 39.1, 26.6 and 31.1 months, respectively. No statistical difference of LRFS, iPFS and OS were found between patients with different numbers of BM. Nevertheless, patients receiving concurrent systemic therapy had significantly longer LRFS (HR=0.35, p=0.002), iPFS (HR=0.57, p=0.044) and OS (HR=0.37, p=0.001), when compared with those receiving SRT alone. By now, intracranial disease progression (iPD) was documented in 59 patients, with original site PD (OPD), new site PD (NPD) and both sites PD (BPD) occurring in 20 (33.9%), 17 (28.8%) and 22 (37.3%), respectively. Among the 59 patients, 19 (32.2%) received second-course SRT (re-SRT) targeting the intracranial progressive tumor lesions and re-SRT led to improved OS2 (22.7 vs 12.1 months, HR=0.29, 95%CI 0.08-0.97, p=0.045), which remained as an independent prognostic factor after multiple-variate Cox analyses. Conclusions: The status of systemic therapy, but not the number of BMs, may impact the survival outcomes of SRT-treated BMs from NSCLC. Some patients may benefit from re-SRT, which warranted future validation.