A specific monitoring program was implemented in the estuaries of Cantabria (northern Spain) in order to assess the medium-term effects (2003-2005) of the Prestige oil spill (POS) on benthic macroinvertebrate communities. A control-impact design was adopted, examining four unaffected and five oil-affected estuaries. High mortalities and significant differences in overall richness and diversity between the control and impacted estuaries were not detected. Some changes in the temporal evolution of species abundance were observed for some key species, but these could not be related to the spillage event. It was not possible to ensure that low magnitude effects had not occurred, due to the high range of natural variability of benthic communities, the confounding effects of other contamination sources and the absence of previous reference conditions.