PURPOSE: Alternating electric fields (AEF) therapy in addition to temozolomide chemoradiotherapy (TMZ CRT) is increasingly being recommended as first-line treatment for patients with newly-diagnosed WHO grade 4 astrocytoma. However, few have validated this treatment with real-world evidence. METHODS: Consecutive adult patients with newly-diagnosed WHO grade 4 astrocytoma treated with adjuvant TMZ CRT across all neuro-oncology centers in Hong Kong were reviewed. Identified from a territory-wide prospective glioma registry, propensity-score matching (1:2) was performed to match patients that either received TMZ CRT with AEF or TMZ CRT alone. Matching was according to age, Karnofsky performance status, IDH-1 mutation, pMGMT methylation and extent of resection. The primary endpoint was overall survival (OS). Secondary endpoints were the incidence of AEF-associated adverse effects and mean monthly treatment compliance. RESULTS: 141 patients were reviewed, of whom 47 patients received AEF with TMZ CRT and 94 had CRT alone. Multivariate Cox proportional hazards analysis revealed that patients with pMGMT-methylated tumors (mOS: 30.8 months vs. 16.7 months [95% CI: 1.9-4.7] and those that received AEF (mOS: 22.8 vs. 14.3 months [95% CI: 1.9-4.7]) had longer OS. AEF therapy patients had a mOS benefit of 8.5 months. The mean monthly treatment compliance was 74 ± 12%. A compliance threshold of 60% conferred a survival benefit of 4.1 months (mOS: 21.5 months vs. 17.4 months [95% CI: 0.10-0.96]). The only identified AEF-associated adverse reaction was scalp dermatitis that occured in 77% (36/47) of patients. CONCLUSION: This post-approval study offers real-world evidence in support of the use of AEF therapy as first-line treatment.