Vigabatrin (GVG) and lamotrigine (LTG) are new antiepileptic drugs (AEDs) individually effective as add-on therapy for refractory seizures. The efficacy of GVG and LTG in combination was evaluated in a prospective audit of 42 patients with intractable epilepsy. There was a statistically significant median reduction of 62% (P < 0.025) from a median baseline monthly seizure frequency (MSF) of 29 (mean 59, 95% CI 22, 96) to a median MSF of 11 (mean 23, 95% CI 8, 38) during a median treatment period of eight months, with a greater than 50% reduction in MSF in 29 patients (69%) treated with the add-on combination of GVG and LTG. The additional MSF reduction achieved by the combination amounted to 21% (18% when GVG was added to LTG and 24% when LTG was added to GVG). The median trough plasma lamotrigine concentration was 9.9 mg/l (range 3.4-19.6 mg/l). The average daily dose of LTG was 517 mg (range, 175-800 mg) and GVG 2400 mg (range, 1500-3500 mg). Adverse events requiring alteration of therapy occurred in 24 patients (57%) with a drop-out rate of 12%. The combination of GVG and LTG should be considered as a therapeutic option in patients with intractable epilepsy. The results of the present study support the need to confirm additive efficacy of GVG and LTG by conducting controlled trials of this combination therapy.