Purpose Motor evoked potentials (MEPs) elicited by a train of consecutive, individual transcranial magnetic stimuli demonstrate fluctuations in amplitude with respect to time when recorded from a relaxed muscle. The influence of time‐varying, instantaneous modifications of the electroencephalography (EEG) properties immediately preceding the transcranial magnetic stimulation (TMS) has rarely been explored. The aim of this study was to investigate the influence of the pre‐TMS motor cortex and related areas EEG profile on time variants of the MEPs amplitude. Method MRI‐navigated TMS and multichannel TMS‐compatible EEG devices were used. For each experimental subject, post‐hoc analysis of the MEPs amplitude that was based on the 50th percentile of the MEPs amplitude distribution provided two subgroups corresponding to “high” (large amplitude) and “low” (small amplitude). The pre‐stimulus EEG characteristics (coherence and spectral profile) from the motor cortex and related areas were analyzed separately for the “high” and “low” MEPs and were then compared. Results On the stimulated hemisphere, EEG coupling was observed more often in the high compared to the low MEP trials. Moreover, a paradigmatic pattern in which TMS was able to lead to significantly larger MEPs was found when the EEG of the stimulated motor cortex was coupled in the beta 2 band with the ipsilateral prefrontal cortex and in the delta band with the bilateral centro‐parietal‐occipital cortices. Conclusion This data provide evidence for a statistically significant influence of time‐varying and spatially patterned synchronization of EEG rhythms in determining cortical excitability, namely motor cortex excitability in response to TMS. Hum Brain Mapp 35:1969–1980, 2014. © 2013 Wiley Periodicals, Inc.