Remote sensing and in situ observations, and model simulations made during the Dynamics of the Adriatic in Real Time (DART) project in the central Adriatic Sea during 2006 reveal intense mesoscale eddy activity in the West Adriatic Current (WAC) system, that flows along the Italian coast. We investigate the origin, scale and rate of evolution of these features, and consider their potential contributions to across-shelf exchange, as a basis for planning future operational coastal prediction and monitoring programs. Predictions from a regional Adriatic Sea implementation of the Navy Coastal Ocean Model (NCOM) are assessed using observations from satellites, current meter moorings, and ship hydrographic transects. Near Cape Gargano in summer, mesoscale eddies and filaments observed in remote sensing imagery and in situ data exhibit horizontal and vertical scales of about 30 km and 25 m, respectively. The observed eddies develop along the WAC front under transient wind conditions, while a quasi-permanent anti-cyclonic circulation appears downstream of the cape. NCOM model predictions show that well-organized, multiple-eddy features appear, grow in unison, then dissipate along the coast west of Cape Gargano in response to transient along-shelf wind forcing, while east of it individual eddies are generated by interaction of the WAC main stream with the bathymetry surrounding the cape. The eddies evolve over time scales of a few days to a week in response to forcing transients. Moderate to strong northwest winds compress the WAC coastward and suppress the instabilities, while relaxing northwest winds or shifts to southeast winds expand the WAC and enhance instability growth. Together with entrained filaments of coastal water, the eddies translate, stretch and rotate in response to WAC horizontal advection and shear. The qualitative character and evolution of the modeled features agree with the observations, and model statistics reveal patterns of variability on monthly and seasonal time scales that are consistent with the appearance of individual eddies in both the model results and observations. In the model, patterns of upwelling and downwelling associated with the WAC main stream and eddies may be linked to dynamical characteristics of the WAC flow and specific bathymetric features. Under wintertime conditions, theoretical arguments predict an upwelling response as flow divergence changes absolute vorticity where the WAC rounds the cape, while Ekman pumping driven by surface winds or bottom stress and associated secondary circulation could explain upwelling and downwelling patches appearing around the rims of individual eddies. The upwelling dynamics are complicated by seasonal stratification effects and bathymetric features, and more work is needed to elucidate these processes. Based on their frequent occurrence, large size compared to the shelf width, high intensity and current shear, and secondary circulations, the eddies and filaments could contribute significantly to across-shelf exchange and coastal/deep-ocean mixing, with important implications for coastal monitoring and prediction. Their generation and evolution present special challenges for coastal prediction, but our results demonstrate that combined use of remote sensing imagery and numerical model simulations can yield valuable insight into such processes, and thereby help plan future monitoring and prediction efforts.