The objective of this study was to compare the efficacy and tolerability of two new antiepileptic drugs, lamotrigine (LTG) and vigabatrin (GVG) in everyday clinical practice. A comprehensive retrospective survey of a computerized data base and hospital case notes was carried out at the Mersey Regional Epilepsy Clinic (MREC), Liverpool, which services a population of 3 million in the North West of England. The study comprised 333 out-patients with refractory epilepsy exposed to LTG and GVG forming a subset in a total population of 2250 patients with epilepsy held on a comprehensive database. The main outcome measures were duration of treatment with each drug described by a Kaplan-Meier survival curve, seizure control determined by a 50% decrease in seizure frequency and freedom from seizures, and incidence of adverse drug effects leading to discontinuation. The Kaplan-Meier curve indicated a 57% probability of patients continuing to take LTG and 43% GVG after 40 months. A 50% improvement in seizure control followed the addition of LTG in 45% of patients, with 10% seizure free, compared with 32% and 6%, respectively after the addition of GVG. LTG was discontinued because of adverse events (most frequently skin rash) in 15% of patients compared to GVG in 25% (particularly because of personality disturbance and psychiatric disorder). Both LTG and GVG are effective new AEDs in patients with refractory epilepsy, treated in a tertiary referral out-patient setting. LTG has a broader spectrum of antiepileptic efficacy for patients with both partial and idiopathic generalized seizures, whereas GVG should be reserved for patients with partial seizures at low risk of psychiatric disorder.