Functional neuroimaging studies have increasingly aimed at approximating neural substrates of human cognitive sex differences elicited by visuospatial challenge. It has been suggested that females and males use different behaviorally relevant neurocognitive strategies. In females, greater right prefrontal cortex activation has been found in several studies. The spatiotemporal dynamics of neural events associated with these sex differences is still unclear. We studied 22 female and 22 male participants matched for age, education, and nicotine with 29-channel-electroencephalogram recorded under a visual selective attention paradigm, the Attention Network Test. Visual event-related potentials (ERP) were topographically analyzed and neuroelectric sources were estimated. In absence of behavioral differences, ERP analysis revealed a novel frontal-occipital second peak of visual N100 that was significantly increased in females relative to males. Further, in females exclusively, a corresponding central ERP component at around 220 ms was found; here, a strong correlation between stimulus salience and sex difference of the central ERP component amplitude was observed. Subsequent source analysis revealed increased cortical current densities in right rostral prefrontal (BA 10) and occipital cortex (BA 19) in female subjects. This is the first study to report on a tripartite association between sex differences in ERPs, visual stimulus salience, and right prefrontal cortex activation during attentional processing. Hum Brain Mapp 2009. © 2009 Wiley-Liss, Inc.