Rationale: Recent years have witnessed a marked improvement in the safety and accuracy of nerve blocks with the help of ultrasound and other visualization technologies. This study reports a challenging case of a severe complication during the ultrasound-guided stellate ganglion block. Patient concerns: A 28-year-old male patient with refractory migraine complained episodic pulsatile pain with photophobia, haphalgesia of the scalp for 3 years. Interventions: Ultrasound-guided stellate ganglion block with 4ml of 1% lidocaine was administrated. Outcomes: A sudden loss of consciousness and tonic-clonic seizure was occurred after negative aspiration and test dose. Further sonographic examination revealed a variation in the left vertebral artery, which remained unrecognized during the needle insertion because of its sliding ability under the differential pressure applied by the probe. Lessons: Inadvertent intra-arterial injection of a local anesthetic agent could be minimized under the ultrasound guidance with various protective strategies, including the determination of any prior variation, optimizing the block route, maintaining a constant probe pressure, and using saline for the test dosage. This case resulted in the implementation of new protocols of the ultrasound-guided stellate ganglion block in our department.