a b s t r a c tProblems considered: Phenytoin is the drug of choice for post operative seizures while some studies have shown lack of efficacy of phenytoin in reducing seizure frequency after craniotomy, which in turn may be due to fall in plasma phenytoin levels after craniotomy. Aims: The aim of the study is to describe changes, if any, in plasma phenytoin levels after craniotomy and its relation to intra operative blood loss. Methods: This was a prospective study in which total of 50 consecutive patients were enrolled after taking written informed consent, who were either on oral phenytoin for at least 7 days or had received intravenous loading dose prior to craniotomy. All patients had serum phenytoin levels monitored 24 h pre operatively, immediately pre craniotomy before skin incision and post craniotomy after skin closure, and 24 h after craniotomy. All patients had intra operative blood loss calculated with help of modification of Gross formula. Results: There was a mean fall of 23.6% in serum phenytoin level immediately following craniotomy which was statistically significant. Furthermore, analysis indicated that greater the operative duration and blood loss, greater was the fall in serum phenytoin level. Conclusions: The study concludes that routine measurement of perioperative serum phenytoin levels in high risk patients may be of benefit in preventing post craniotomy seizures and an additional bolus dose should be given towards the end of surgery to patients with significant intra operative blood loss. ScienceDirect journal homepage: www.elsevier.com/locate/ijnt t h e i n d i a n j o u r n a l o f n e u r o t r a u m a 1 1 ( 2 0 1 4 ) 1 0 9 e1 1 2 http://dx.