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Although small in size, the Gulf of Trieste (GoT), a marginal coastal basin in the northern Adriatic Sea, is characterized by very complex dynamics and strong variability of its oceanographic conditions. In April–May 2012, a persistent, large-scale anticyclonic eddy was observed in the GoT. This event was captured by both High Frequency Radar (HFR) and Lagrangian drifter observations collected within the European MED TOSCA (Tracking Oil Spill and Coastal Awareness) project. The complexity of the system and the variety of forcing factors constitute major challenges from a numerical modeling perspective when it comes to simulating the observed features. In this study, we implemented a high-resolution hydrodynamic model in an attempt to reproduce and analyze the observed basin-wide eddy structure and determine its drivers. We adopted the Massachusetts Institute of Technology General Circulation Model (MITgcm), tailored for the GoT, nested into a large-scale simulation of the Adriatic Sea and driven by a tidal model, measured river freshwater discharge data and surface atmospheric forcing. Numerical results were qualitatively and quantitatively evaluated against HFR surface current maps, Lagrangian drifter trajectories and thermohaline data, showing good skills in reproducing the general circulation, but failing in accurately tracking the drifters. Model sensitivity to different forcing factors (wind, river and tides) was also assessed.