The spread of the introduced chlorophyte alga Caulerpa racemosa (with its variety cylindracea) in the Mediterranean Sea has been dramatic in the past decade due to its ability to cover substantial bottom areas and modify invaded habitats. From its first appearance in the mid-1990s, C. racemosa var. cylindracea has proliferated along the soft bottom of the Gulf of Salerno (Tyrrhenian Sea), which in its central part was largely unvegetated. A long-term assessment of the macrofaunal assemblages from this area was conducted based on a comparison between a historical dataset of macrofaunal species and abundances obtained in 1981, before the introduction of the alga, and datasets derived from sampling performed in 2006 and 2007 at the same stations. The aim of the comparison was to explore whether a detectable change occurred in the degree of diversity and in the composition of macrofaunal assemblages and, if this occurred, whether such change could be attributed, at least in part, to the C. racemosa colonization in the area. Although overall local diversity did not change in the study area, the composition of the macrofaunal assemblages in 2006–2007 differed from that in 1981. The most conspicuous changes were a decline in infaunal bivalve molluscs and an increase of mobile epibenthic forms (notably the mollusc Nassarius pygmaeus); these may be linked to the influence of C. racemosa on sediment properties. The dominance of some species (mainly polychaetes) may be associated with other environmental factors such as the intensity of riverine inputs. The impact of the invasive alga appears to vary according to the habitat invaded.