The risk of dose-dependent seizures is a safety issue with bupropion hydrochloride. To evaluate the presence of specific electroencephalographic (EEG) waveforms, 210 adult subjects taking stable doses of bupropion hydrochloride were recruited to undergo 2 EEGs in a prospective, single-center cohort study. The occurrence of spike waves, sharp waves, and focal slowing was recorded and assessed with a continuation ratio logit model for polytomous responses. This model showed that there was a relationship between sex and the incidence of these waveforms, such that the odds of female subjects having sharp waves was increased by a factor of 2.53 (P = 0.05) when compared with male subjects and controlled for both age and dose. Similarly, female subjects were 2.45 (P = 0.09) times more likely than males to have focal slowing on EEG. Overall, 19.8% (39/197) of this representative population was found to have abnormal, asymptomatic EEG findings. The presence of these waveforms in individuals taking a medication known to lower the seizure threshold may be a risk factor for developing seizures.