Introduction: Patients with HER2-positive metastatic breast cancer are at risk for developing brain metastases. Different anti-HER2 treatments can be used in the management of the disease. In this study, we aimed to evaluate the prognosis and the factors affecting the prognosis in brain metastatic patients with HER2-positive breast cancer. Methods: Clinical and pathological features of HER2-positive metastatic breast cancer patients and magnetic resonance imaging features at the onset of brain metastasis were recorded. Survival analyses were performed using Kaplan-Meier and Cox regression methods. Results: Analyses of the study were performed by including 83 patients. The median age was 49 (25–76). All patients had HER2 receptor-positive tumors. Thirty-five (42.2%) patients had a hormone-positive disease. Thirty-two (38.6%) patients had de novo metastatic disease. Brain metastasis sites were found to be bilateral – 49.4%, right brain – 21.7%, left brain – 12%, and unknown – 16.9%, respectively. The median brain metastasis largest size was 16 mm (range 5–63). The median follow-up time from the post-metastasis period was 36 months. Median overall survival (OS) was found as 34.9 months (95% CI, 24.6–45.2). In multivariate analysis for factors affecting OS, estrogen receptor status ( p = 0.025), number of chemotherapy agents used with trastuzumab ( p = 0.010), number of HER2-based therapy ( p = 0.010), and the largest size of brain metastasis ( p = 0.012) were found to be statistically significant. Conclusions: In this study, we demonstrated the prognosis in brain metastatic patients with HER2-positive breast cancer. When the factors affecting the prognosis were evaluated, we determined that the largest size of brain metastasis, estrogen receptor positivity, and the use of TDM-1 and lapatinib plus capecitabine consecutively during the treatment process affected the prognosis of the disease.