Status epilepticus (SE) and seizure clusters (SCs) are emergency situations, which require immediate and effective treatment. This study aimed to investigate the efficacy and tolerability of intravenous (IV) administration of Valproic acid (IV VPA) in the treatment of SE and SCs. All patients treated in our department with IV VPA between January 2009 and February 2010, were retrospectively analyzed. Indications for IV VPA were SCs and SE refractory to first line therapy (benzodiazepines). Dose, responsiveness and adverse events were evaluated. 31 patients (19 males and 12 females, median age 54.2 years), were included in the study. Twenty one patients presented primary generalized SCs, 6 had focal motor status epilepticus and 4 had focal seizures with secondary generalization. All had previously been unsuccessfully treated with intravenous infusion of Diazepam. The treatment protocol implied a 25mg/kg b.w. of IV VPA loading dose over 30 minutes, followed by continuous infusion of 100 mg/h for at least 24h, continued by oral administration. In 80% of the cases (25 of 31), seizures stopped within 6 h, and general anesthesia was not required. Four patients (12%) required general anesthesia and 2 patients were resistant to all therapeutic attempts and died. SE was symptomatic in all cases, 16 with stroke, traumatic 6, toxic 4, infectious 3 and tumors 2. No serious side effects were reported considering that relevant medical history included cardiac arrhythmias, respiratory distress and hepatic disease. IV VPA proved to be a safe, effective treatment of status epilepticus and SCs, especially in patients with co-morbidities (cardiovascular diseases and respiratory insufficiency).