Recent evidence suggests that attributes of the ictal electroencephalogram (EEG) may be clinically useful for estimating the extent to which the electroconvulsive therapy (ECT) stimulus exceeds the seizure threshold (relative stimulus intensity). Such a tool could allow a practitioner, who chose, on the basis of expected therapeutic response and side effect rates, to implement stimulus dosing to maintain relative stimulus intensity over the treatment course, despite the uncertain rise in seizure threshold that occurs. One potential confounding factor is a possible systematic change in the ictal EEG over the treatment course that is not due to changes in seizure threshold. We explored the effect of treatment number by comparing ictal EEG data obtained at treatments across the ECT course that were delivered at the identical relative stimulus intensity. We found that the ictal EEG at treatment 1 was characterized by a greater mid-ictal amplitude and post-ictal suppression (trend) than subsequent treatments for barely suprathreshold unilateral ECT, but not for barely suprathreshold bilateral or moderately suprathreshold unilateral ECT, and that this change may affect therapeutic effectiveness. These findings suggest the importance of treatment-number effects for the clinical application of the ictal EEG and point to possible physiological differences between unilateral and bilateral ECT.