In a randomized crossover study, the influence of the anesthetics methohexital and propofol on EEG seizure parameters, seizure-quality measures, vital signs, and oxygen saturation (Spo2) and end-tidal carbon dioxide tension (ETco2) was investigated; 146 treatments of 31 patients were analyzed. Significant differences were observed between agents for mean postictal pulse and blood pressure values. With methohexital, there was a clear postictal increase of mean blood pressure from 126/78 mm Hg to 161/102 mm Hg, whereas there was no increase with propofol (p = 0.00), and with methohexital, a postictal increase of the mean pulse rate from 81 to 90 beats/min and a slight decrease with propofol (79 to 78 beats/min). There were no differences in the Spo2 and ETco2. The mean seizure duration for unilateral treatments was significantly longer with methohexital (52.7 s) compared with propofol (34.1 s; p = 0.000), but there was no difference for the seizure-quality measures: postictal suppression index (propofol 79.7%, methohexital 77.4%) and mean integrated amplitude (30.2/31.8) were the same for both anesthetic agents. The results show that differences in seizure duration are unrelated to seizure-quality measures.