- We investigate the effect of interannual variability of the wind-stress over the Eastern Mediterranean on Adriatic Deep Water (ADW) formation using an oceanic general circulation model of the Mediterranean Sea driven by monthly ERA-Interim wind-stress of the years 1979–2014. This is done by using climatological annual cycle of the surface temperature and freshwater flux but interannually varying wind-stress. A connection between the wind-stress magnitude over the Rhodes Gyre region and ADW outflow is found in association with the formation of Levantine Intermediate Water (LIW). 720 years artificially generated wind-stress fields were constructed based on the first 50 Empirical Orthogonal Functions (EOFs) of the wind-stress monthly anomalies. This simulation strengthen the connection that was found and also reveal a centennial internal variability of both the LIW and the ADW outflow. It is also found that the intensity of the Rhodes Gyre is almost linearly related to the wind-stress amplitude. However, the ADW outflow is non-monotonically related to the wind-stress amplitude. There is an optimal wind-stress amplitude for which the ADW formation is maximal. When the wind-stress amplitude is more than 50% the climatological mean wind-stress amplitude, the ADW outflow is weakened. This implies a different balance between the saline LIW and the fresh Atlantic Water, entering the Eastern Mediterranean from Sicily Strait, under stronger than present wind-stress amplitude.