Patients with large variations in phenytoin levels despite standard doses may prove to become difficult clinical problems. Our study of 34 head injury patients whose serum phenytoin levels were measured on day one and day five following intravenous loading and maintenance dose of phenytoin, showed 38.24% patients, to have therapeutic phenytoin levels on day one, while 20% were in toxic range. On day five, 23% patients were in toxic and 29.41% were in therapeutic range. Only 21% patients remained in the therapeutic range during the monitoring period. This study shows that there is a wide variability of phenytoin levels in the ICU patients with a difference of more than 100% between the highest and lowest phenytoin level in individual cases (in four patients the difference exceeded 500%) raising concern about the safety of the drug. Hence it is recommended that intensive care unit patients receiving phenytoin therapy should have periodic serum phenytoin obtained even in absence of seizures or classic signs phenytoin toxicity.