The goal of this paper is to investigate the relationship between environmental variables and the occurrence of anchovy (Engraulis encrasicolus) spawning over a year, in order to enable the timing and strength of high spawning activity to be predicted. Biological sampling of anchovy was conducted on the fishing grounds of the eastern Adriatic (the northernmost semi-enclosed basin in the Mediterranean) on a monthly basis from January 1999 to December 2010, while data on environmental parameters were taken from in situ measurements at the most representative and best surveyed eastern Adriatic hydrographic station and from I-COADS monthly surface fields. Anchovy spawning seasonality was defined by monthly changes of the maturity stages and the gonadosomatic index. Fluctuations of the gonadosomatic index revealed that spawning begins in March and lasts until September, with reproductive activity peaking from April to July. A significant correlation was found between the gonadosomatic index and upper layer salinity in the two preceding months, while the lagged wind-mixing index and surface temperature are barely correlated to the gonadosomatic index. An enhanced input of nutrient-rich freshwater of river origin, which reduces upper layer salinity and enhances primary production up to 2 months before anchovy spawning, seems to be correlated with the anchovy fertility, especially for a late spawning maximum (in July).