BACKGROUND The evidence based data to guide management in patients of benzodiazepine refractory status epilepticus (SE) is still lacking. We conducted a randomized study to evaluate the comparative effect of intravenous (IV) phenytoin and intravenous valproate (IV VA) in patients of benzodiazepine refractory SE. METHODS Hundred, age and sex matched, patients of benzodiazepine refractory SE were randomly divided into Group A (50 patients), treated with IV VA and Group B (50 patients) treated with IV phenytoin. Twelve patients, in whom SE was not controlled with a single drug, were switched over to the other group. Treatment was considered successful when all motor or EEG seizure activity ceased within 20 min after the beginning of the drug infusion and no return of seizure activity during the next 12h. Secondary study end points were adverse events to treatment, in-hospital complications and the neurological outcome at discharge. RESULTS In this study, IV VA was successful in 88% and IV phenytoin in 84% (p>0.05) of patients of SE with a significantly better response in patients of SE <2h (p<0.05). The total number of adverse events did not differ significantly between the two groups (p>0.05). There were no differences among the treatments with respect to recurrence after 12-h study period or the outcome at 7 days. CONCLUSIONS IV VA is as effective as IV phenytoin. It is easy to use, better tolerated and can be used as an alternative to IV phenytoin in patients of benzodiazepine refractory SE, especially in patients of cardio-respiratory disease. The better outcome in patients having shorter duration of SE (<2h) suggests need of immediate treatment.