This study examines the seismicity of Vesuvius in the decades leading up to the great eruption of 16th December 1631. The period 1600–1631 is analyzed with the aims to point out any long-term seismic precursor of the eruption. The historical research has focused on contemporary Neapolitan memoirs and a large screening of diplomatic correspondence from the main Italian courts of the age (Florence, Mantua, Parma, Venice and the Vatican). Information was gathered on 18 earthquakes that were felt in Naples between 1601 and 1630. These data were listed with the sequence of 34 shocks that took place in November and December 1631, that preceded the beginning of the eruption. The 52 seismic events that have been highlighted overall are unknown in the parametric catalogues of Italian historical seismicity and 17 are unknown even in the scientific literature. The authors' view is that it makes little sense to talk of one single previous seismic precursor in this case, given the frequent seismic sequences and tremors noted by contemporaries from January 1616 onwards. The present state of knowledge suggests that seismic activity is a strong, early and persistent warning sign of an eruption of Vesuvius, of the same type as that of December 1631.