Pentobarbital and propofol are used for the treatment of refractory status epilepticus or elevated intracranial pressure, typically with continuous EEG monitoring. We report a series of patients who developed generalized periodic discharges related to anesthetic withdrawal (GRAWs), different from previous seizure activity. At times, this pattern was misinterpreted as recurrent seizure activity, leading to reinstitution of drug-induced coma, but resolved spontaneously without additional treatment.We identified five patients who developed GRAWs during pentobarbital or propofol withdrawal. Two patients received pentobarbital for increased intracranial pressure. One patient received pentobarbital and propofol for encephalopathy accompanied by a rhythmic EEG pattern erroneously thought to be ictal. Two patients received pentobarbital for refractory partial status epilepticus. In all cases, anesthetic agents were withdrawn after 24 to 48 hours of burst suppression on EEG. We analyzed the course of GRAWs on EEG and the associated clinical outcomes.All five patients developed GRAWs, consisting of periodic 1 to 4 Hz generalized periodic discharge, not previously seen on EEG. In all cases, the pattern eventually resolved spontaneously, over 12 to 120 hours. However, in three cases, the pattern was initially thought to represent ictal activity, and drug-induced coma was reinitiated. The pattern recurred during repeated anesthetic withdrawal, was then recognized as nonictal, and then resolved without further treatment. In all cases but one, the patients exhibited improvement to near-baseline mentation.Generalized periodic discharges related to anesthetic withdrawal may occur de novo after pentobarbital or propofol withdrawal. They should resolve spontaneously without treatment and without recurrence of clinical seizure activity. However, GRAWs are not likely to represent status epilepticus and should not prompt resumption of drug-induced coma, unless there is reappearance of original electrographic seizure activity.