It was previously shown that variation of the catechol-O-methyltransferase (COMT) gene modulates brain activity during the processing of stimuli with negative valence, but not for pleasant stimuli. Here, we tested whether the COMT genotype also modulates the electrophysiological correlates of emotional processing and explored whether the environmental factor of life stress influences this effect. Using the early posterior negativity (EPN) paradigm, event-related brain potentials were measured in 81 healthy individuals during the processing of pictures that evoked emotions of positive and negative valence. As was hypothesized, the COMT genotype affected the EPN amplitudes for unpleasant stimuli, but not for pleasant ones. Specifically, Met/Met carriers respond more sensitively to unpleasant stimuli, as compared with Val/Val carriers. We did not find evidence that life stress moderates the effect of the COMT genotype on emotional stimuli processing.