Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit).