Interannual variability of the primary production in the middle Adriatic Sea for the period 1961–2002 was examined and correlated to the various atmospheric and oceanographic parameters. The sequential t-test analysis of regime shift (STARS) method and locally-weighted scatter plot smoothing (LOWESS) method were applied to the primary production, revealing the new regime with significantly different mean productivity ranging from 1980–1996. Moreover, this period with the highest primary production, consists of the two distinguished sub-periods: periods of increasing (1980–1986) and decreasing (1987–1996) primary production. Whereas in the first period the ecosystem was under the influence of warmer and nutrient richer Levantine Intermediate Water (LIW) intrusions into the Adriatic, in the second period, which started with a cold winter in 1987, the Eastern Mediterranean Transient (EMT) occurred. The EMT established a new circulation regime which prevented the LIW intrusions in the Adriatic, causing its reduced productivity. Reduced LIW inflow in the Adriatic was evidenced in the lower than normal sea temperature, salinity and oxygen concentrations below the thermocline depth. Precipitation and wind regime also arose as important local factors for the primary production variability. Our analysis connected the shifts in primary production with hemispheric and regional scale climate variations, and supports the hypothesis that atmospheric variability can trigger the ecosystem changes.