Background: In 25-55% of Human epidermal growth factor receptor type 2 (HER2+) metastatic breast cancer (MBC) patients, central nervous system metastases will occur. Herein we describe treatment patterns and clinical outcomes in a modern series of patients with HER2+ MBC with brain metastases in a population based cohort of Maccabi Healthcare Services in Israel. Methods: Patients aged ≥18 years, who initiated first-line treatment for metastatic HER2 positive breast cancer between 1^st January 2013 until 30^th June 2021 and received brain surgery and/or irradiation were identified and followed until December 2021. The index date was fixed as the first day of first-line treatment. Time on treatment (ToT, as a surrogate for progression-free survival) and overall survival (OS) were determined. Results: A total of 61 patients with HER2+ MBC and brain metastases were identified. Median theoretical follow-up time was 6.2 years. The cohort consisted of 98.4% females, median age 50 years (IQR: 44-63), tumors were invasive ductal in 85% and in 57% were hormone receptor positive; ECOG performance status was 0-1 in 51% and missing in 32%. All patients initiated tratuzumab-pertuzumab-chemotherapy (TPC) combination, and second-line treatment was started in 72% during study follow up. Median ToT for first and second-line treatments were 16.9 months (95% CI: 13.9-27.7) and 7.92 months (5.6-10.9), respectively. In 15 patients (25%) brain metastases were diagnosed prior to TPC or within 6 months of treatment initiation, in 25 patients (41%) while on TPC treatment, and in 21 (34%) at later periods. Median OS was 45.5 months (35.4-71.2) from initiation of first-line treatment, and 36.3 months when brain metastases occurred upfront, 59.1 months when diagnosed while on TPC, and 40.8 months when diagnosed later. Median OS from brain metastases diagnosis was 25.1 months (17.0-34.6). Conclusions: We provide ToT (as surrogate for PFS) and OS on HER2+ MBC patients with brain metastases treated with upfront TPC in first line setting and mostly TDM1 in second line setting in a real-world setting. Outcome with newer anti-HER2 directed regimens for patients with brain metastases should consider clinical findings in this relatively modern series.