As standard rTMS protocols exhibit after-effects of short duration and show limited efficacy as therapeutic intervention in psychiatric and neurological disorders, novel protocols, e.g. theta burst stimulation (TBS), have been developed for motor cortex stimulation and are promising approaches to enhance the effectiveness of rTMS. However, little is known about the side effect profile of such protocols. Thus, the present study investigates whether TBS is safe in terms of side effects and has effects on cognition and EEG measurements. Within two exploratory placebo-controlled, cross-over studies, 24 healthy volunteers underwent continuous TBS (cTBS), intermittent TBS (iTBS) and sham TBS over the left dorsolateral prefrontal cortex (DLPFC, N=12) or the medial prefrontal cortices (mPFC, N=12) in random order. Side effects, resting EEG, performance in a neuropsychological test battery and mood were recorded. All protocols proved to be safe in terms of seizure generation. The most prominent side effect was the occurrence of vasovagal reactions after TBS. Standardized low resolution brain electromagnetic tomography (sLORETA) showed changes in current source density of different frequency bands in the frontal lobe with simultaneous effects in neuropsychological data. Although TBS protocols of the human prefrontal cortex appear to be rather safe, future studies need to explain the occurrence of vasovagal reactions with TBS. The excitatory and inhibitory mechanisms of TBS reported for the motor cortex are not easily transferable to prefrontal sites. Moreover, TBS seems to exert long lasting effects after iTBS over the left DLPFC.