Background <p>Teprotumumab is the only FDA-approved medication for thyroid eye disease (TED), showing benefits in reducing proptosis, diplopia, clinical activity score (CAS), and improving quality of life. This study describes the clinical outcomes of TED patients treated with Teprotumumab across 5 medical centers in Israel and evaluates time-to-improvement.</p> Methods <p>A retrospective cohort study of electronic medical records for Israeli patients treated with Teprotumumab between 2021 and 2024 in five medical centers. The main outcome included changes in proptosis and diplopia.</p> Results <p>Thirty-two TED patients (mean age 53.3, 19 females) received partial or complete treatment with Teprotumumab. All had previously failed IV glucocorticoids, and some also failed other biologics. Four patients had decompression surgery prior; 3 with optic neuropathy and 1 with proptosis improved after 1–7 doses. Proptosis decreased by 2.4mm (right) and 2.0mm (left) (<i>p</i> &lt; 0.001, <i>p</i> = 0.002, paired sample <i>t</i>-test), with significant reductions in primary gaze diplopia (<i>p</i> = 0.015, chi-square test). Four patients (12.5%) had symptom recurrence 8–12 months post-treatment; one improved with additional treatment. Thirteen patients (40.6%) had significant improvement within 3 infusions. Adverse events included myalgia (<i>n</i> = 4), hyperglycemia (<i>n</i> = 3), diarrhea (<i>n</i> = 3), and hearing issues (<i>n</i> = 4). One patient developed encephalopathy, successfully treated with plasmapheresis.</p> Conclusions <p>Teprotumumab was effective in reducing diplopia and proptosis among Israeli TED patients, with rapid improvement in nearly half of the cases. Further studies are warranted to confirm these findings in real-world settings.</p>