Abstract Introduction: Tumor Treating Fields (TTFields) are an antineoplastic treatment delivering low-intensity, intermediate-frequency, alternating electric fields through 2 pairs of transducer arrays locoregionally applied to tumor bed. TTFields are FDA-approved for glioblastoma (GBM; 200 kHz) and mesothelioma (150 kHz). Safety and effectiveness were demonstrated in the Phase 3 EF-11 and EF-14 trials in recurrent GBM (rGBM) and in newly diagnosed GBM (ndGBM), respectively. The main TTFields-related adverse event (AE) was array-associated manageable scalp irritation. We report AEs from TTFields-treated patients in the real-world, clinical practice setting. Methods: Unsolicited, global, post-market surveillance data from TTFields-treated patients (October 2011-February 2019) were retrospectively analyzed using MedDRA v21.1, stratified by region (US, EMEA [Europe, Middle East, Africa], or Japan), diagnosis (ndGBM, rGBM, anaplastic astrocytoma, anaplastic oligodendroglioma, or other brain tumors [includes brain metastases from different cancer types]), and age (years; <18 [pediatric], 18 to 64 [adults], or ≥65 [elderly]). Results: Of 11,029 patients, 53% had ndGBM, 39% had rGBM (at any line of recurrence), 6% had anaplastic astrocytoma/oligodendroglioma, and 1% had other brain tumors. Most were adults (73%) and 26% were elderly (≥65 years of age). The majority of patients was males (n=7313; 66.3%) compared to females (n=3716; 33.7%). The most commonly reported TTFields-related AE was array-associated local skin reaction, with an incidence of 38% in ndGBM, 29% in rGBM, 38% in anaplastic astrocytoma/oligodendroglioma, 31% in other brain tumors, 37% in pediatric, 34% in adults, and 36% in elderly patients. Most skin AEs were grade 1 and 2 and they were reversible with treatment. Other TTFields-related AEs in patients with ndGBM and rGBM, respectively, included heat sensation (under-array warmth; 11%, 10%), electric sensation (under-array tingling; 11%, 9%), and headache (7%, 6%). Conclusions: This retrospective, global, TTFields safety surveillance analysis revealed no new safety signals, with favorable safety and tolerability comparable to published TTFields/GBM trials. The most common TTFields-related AE was array-associated local skin reaction. The safety profile remained consistent among subgroups (diagnosis, age, or region) and total cohort, indicating feasibility in multiple subpopulations, including elderly patients. Citation Format: Wenyin Shi, Deborah T. Blumenthal, Nancy Ann Oberheim Bush, Sied Kebir, Rimas V. Lukas, Yoshihiro Muragaki, Jay-Jiguang Zhu, Martin Glas. Post-marketing safety surveillance of Tumor Treating Fields (TTFields) in patients with high-grade glioma in clinical practice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-167.