OBJECTIVES: To estimate health care costs of patients with partial refractory epilepsy (PRE) in the Mexican Institute of Social Security (IMSS). METHODS: PRE requires long-term health costly care with two or more anti-epileptic drugs, presence of intolerance and side effects. Case series with PRE diagnosis in four hospitals in Mexico City which inclusion criteria were: aged 12 and older, using two or more anti-epileptic drugs and information available of at least one-year follow-up period. Cost evaluation perspective was that from services provider, time horizon was one year and three costing techniques were combined: micro-costing, average cost and cost per diem, using a bottom-up aproach. Costs are expressed in 2004 USD. RESULTS: From medical records (813), 133 were correctly diagnosed as PRE and 72 cases met inclusion criteria. Demographic characteristics: 58% were females, 64% were between 12-35 years old, 47% students, 58% single and 73% had intermediate or preparatory education. Fifty one percent had simple partial seizures and 94% more than one crisis per month. Mean annual visits per patient to general practitioner was 5.2 and to neurologists 6.8; laboratory tests 6.0 and electroencephalographic studies 0.8. Total annual cost of health care was $2646 per patient and 24% was derived from hospitalisation. Total cost was distributed in: 39% visits, 24% drugs, 21% bed days and 16% diagnostic tests. First line drugs were Carbamazepine and Valproic acid (more than 68%), while second line ones Clonazepam (36%), Lamotrigine (33%) and Topiramate (21%). CONCLUSIONS: Most of patients were young, in productive age and had more than one seizure per month; this is a matter of concern because a difficult seizure control affects negatively patient and family social life, including employment. Effectiveness, safety and cost of available drugs are crucial issues in control and quality of life of PRE patients.