OBJECTIVES: Approximately 50% of patients do not achieve seizure control with a single antiepileptic drug (AED). With the advent of multiple AEDs in the past 15 years, the choice of optimal polytherapy remains difficult in absence of clinical studies about the effectiveness of various combination therapies. This study aimed at describing the current management of focal epilepsy treated by polytherapy in France and at estimating the extra-costs of pharmacoresistance (PR) as redefined in 2009 by the International League Against Epilepsy (ILAE). METHODS: ESPERA is a European multicenter, observational, cross-sectional study conducted in France and Spain in 2010. A random sample of neurologists enrolled prospectively a sample of adult patients treated with at least two antiepileptic drugs (AEDs) in combination for focal epilepsy. The investigators classified their patients according to the new ILAE criteria and this classification was then reviewed by two independent experts. All items of medical resources use associated with epilepsy were collected retrospectively over the last year and valued according to a societal perspective. RESULTS: Seventy-one French neurologists collected analysable data on 405 patients. After review by experts, patients were finally classified as PR in 286 (70.6%) of them, in 91 (22.4%) as responsive and in 28 (7%) as undefined. The mean annual epilepsy related direct costs par patient were 4238 € (SD: 3772) in PR patients as compared with 1907€ (SD: 1,739) in responsive patients. AEDs costs were estimated 2602€ and 1544€ respectively and PR patients were significantly more often hospitalized (mean annual cost: 1023€ versus 78€) and had more procedures (mean annual cost: 194€ versus 53€). CONCLUSIONS: Despite the number of therapeutic alternatives available in epileptic patients, a large proportion of them remain with uncontrolled seizures yielding to significant extra costs.