High-flow arteriovenous malformations (AVM) are uncommon vascular anomalies that may lead to significant morbidity, and management becomes challenging when curative interventions are not feasible. Here, we report a 46-year-old man with a refractory upper-limb AVM who experienced rapid improvement in pain and function under thalidomide 50 mg/day, with a reduction in shunt flow (3.0 to 2.2 L/min). Treatment was discontinued after six months due to non-severe adverse effects, while benefits persisted at one year. A literature search identified few case reports, all showing consistent symptomatic improvement and mainly dose-dependent, reversible toxicity. Thalidomide could represent a useful adjunct for selected high-flow AVM resistant to standard therapy, although controlled studies are required.