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Background Refractory headache disorders, including chronic migraine and selected secondary headache syndromes, remain a major therapeutic challenge despite advances in pharmacologic therapies. Emerging endovascular strategies targeting the middle meningeal artery (MMA), including intra-arterial lidocaine infusion and MMA embolization, have been proposed as novel approaches based on modulation of trigeminovascular pathways.Purpose To systematically evaluate the available evidence on MMA-directed endovascular therapies for refractory headache, focusing on efficacy signals, durability of response, and safety.Methods A systematic review was conducted in accordance with PRISMA guidelines across PubMed, Embase, and Web of Science. Studies reporting clinical outcomes following intra-arterial lidocaine infusion or MMA embolization for refractory headache were included. Studies in which headache outcomes were primarily attributable to acute intracranial hemorrhage or chronic subdural hematoma were excluded from quantitative synthesis. Due to anticipated clinical and methodological heterogeneity, analyses were stratified by intervention type, and pooled estimates were interpreted as exploratory. Primary outcomes included early headache response, change in headache frequency, and validated disability scores (HIT-6, MIDAS). Secondary outcomes included procedure-related complications.Results Eight studies comprising 104 patients (mean age 52.7 years; 64% women) were included in the quantitative synthesis. Early headache improvement at 24 hours demonstrated pooled responder rates of 93.16% (95% CI: 81.89-100.0%) for ≥30% improvement and 84.91% (95% CI: 70.90-98.93%) for ≥50% improvement. The pooled mean reduction in HIT-6 scores from baseline to last follow-up was 24.15 points (95% CI: 16.03-32.27), and MIDAS scores decreased by 57.67 points (95% CI: 38.08-77.25). A ≥50% reduction in monthly headache days was observed in 60% of patients, and opioid-free headache control was achieved in 53.70%. Procedure-related complications occurred in 3.72% (95% CI: 0.00-8.10%), with no reported permanent neurological deficits. Three illustrative cases were included. Qualitative synthesis demonstrated that intra-arterial lidocaine was associated with rapid but variably durable relief, whereas MMA embolization showed signals of more sustained benefit in select cohorts, although results were heterogeneous.Conclusions MMA-directed endovascular therapies demonstrate a preliminary signal of efficacy in refractory headache; however, the current evidence is limited by small, uncontrolled, and heterogeneous studies. These findings should be considered hypothesis-generating. Well-designed prospective studies are required to better define patient selection, optimize technique, and establish comparative effectiveness and safety.Disclosures J. Alzate Ramirez: None. S. Joao Paulo: None. M. Ferreira: None. V. Ohannesian: None. L. Cheidde: None. L. Campos: None. O. de Araujo: None. C. Ferreira: None. D. Chong: None. S. Azhar: None. Y. Serulle: None.