Over the last decade, there has been increasing evidence for syllabic processing during visual word recognition. If syllabic effects would prove to be independent from orthographic redundancy, this would seriously challenge the ability of current computational models to account for the processing of polysyllabic words. Three experiments are presented to disentangle effects of the frequency of syllabic units and orthographic segments in lexical decision. In Experiment 1 we obtained an inhibitory syllable-frequency effect that was unaffected by the presence or absence of a “bigram trough” at the syllable boundary. In Experiments 2 and 3 an inhibitory effect of initial syllable-frequency but a facilitative effect of initial bigram-frequency emerged when manipulating one of the two measures and controlling for the other in Spanish words starting with CV-syllables. We conclude that effects of syllable-frequency and letter cluster frequency are independent and arise at different processing levels of visual word recognition. Results are discussed within the framework of an interactive activation model of visual word recognition.