The aim of this study was to evaluate the efficacy of lamotrigine, a glutamate antagonist blocking voltage-sensitive sodium channels, in the prophylaxis of migraine aura symptoms. Glutamate is one of the main neurotransmitters involved in the development of cortical spreading depression. The study was conducted as an open longitudinal trial over 7 months, with a treatment phase of 4 months and a post-treatment period of 3 months. Thirteen patients suffering from migraine with aura and 2 patients with aura but without migraine were enrolled and treated with lamotrigine. The dose was gradually increased in steps of 25 mg up to 100 mg per day, depending on the patient's aura symptoms. Aura symptoms were reduced from baseline (an average of 1.3 aura episodes per month) to month 4 (0.1, p < 0.001). High statistical significance was also observed with regard to aura duration (23 min at baseline vs 4 min at 4 months, p < 0.001). In all 15 cases, increases in aura frequency (on average sevenfold, p < 0.001) and aura duration (minutes; on average more than threefold, p < 0.001) were evident following cessation of treatment. A number of mild to moderate adverse events without any medical consequences occurred. The study outcome suggests that lamotrigine is effective in preventing migraine aura symptoms and in influencing migraine headache frequency.