INTRODUCTION: Whole-brain radiotherapy simultaneous integrated boost intensity-modulated radiotherapy (WBRT + SIB-IMRT) is a potential treatment approach for brain metastasis (BM) that may result in improved overall survival (OS). However, the safety and efficacy of WBRT + SIB-IMRT combined with anlotinib for BM treatment remain uncertain. METHODS: We retrospectively compared the safety and efficacy of anlotinib + WBRT + SIB-IMRT with those of WBRT + SIB-IMRT in patients with BM from 2019 to 2022. The adverse reaction type and grade, intracranial objective response rate (iORR), intracranial disease control rate (iDCR), OS, and intracranial progression-free survival (iPFS) of anlotinib + WBRT + SIB-IMRT were compared with those of WBRT + SIB-IMRT alone. RESULTS: In total, 63 patients received either anlotinib + WBRT + SIB-IMRT or WBRT + SIB-IMRT alone (n = 31 and 32, respectively). No significant clinical differences were found between the two groups. The iORR and iDCR were higher in the anlotinib + WBRT + SIB-IMRT group than in the WBRT + SIB-IMRT group. The median iPFS and median OS of the 31 patients who received anlotinib + WBRT + SIB-IMRT were 14.5 and 18.9 months, respectively, whereas the median iPFS and median OS for the 32 patients who received WBRT + SIB-IMRT alone were 11.4 and 14.9 months, respectively. Thus, anlotinib combined with WBRT + SIB-IMRT increased the duration of iPFS, but not OS. iPFS was influenced by the Karnofsky Performance Status (KPS) score, age, extracranial distant metastasis, and addition of anlotinib to treatment, whereas OS correlated with age, extracranial distant metastasis, and KPS score. No treatment-related adverse events of grade 3 or higher occurred in either group. CONCLUSIONS: Anlotinib combined with WBRT + SIB-IMRT is effective for BM and is well tolerated by patients.