Objective To investigate how the ketogenic diet influences the plasma concentrations of valproic acid within 6 months of treatment in pediatric population with drug-resistant epilepsy. Methods The blood levels of valproic acid were investigated in an open study on 37 consecutive children, aged between 8 months and 10 years (mean age 4years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of valproic acid were determined 6 months and immediately before the diet and the first month of treatment and then every month. The daily dose of valproic acid was not changed during 6 months of treatment. Results The level-to-dose ratios of valproic acid before and during the diet were compared, the plasma concentrations of valproic acid showed a slight but not significant decrease (mean decrease of 2.5±1.6), 6 months after the start of the diet. Of the 37 patients enrolled, 31(84%) completed the 6 months follow-up, 6 patients became seizure free, 15 patients had ＞50% seizure reduction and 10 had no change. Conclusion The ketogenic diet does not change the plasma concentrations of valproic acid in children. Therefore, when intiating the diet, it does not seem necessary to adjust drug doses due to pharmacokinetic interactions. The ketogenic diet is a effective alternative therapy for children with drug-resistant epilepsy.