The eastern and western Mediterranean Seas are connected by the Strait of Sicily. The mean flow conditions comprise a near-surface flow of Atlantic Water (AW) into the eastern Mediterranean and an outflow of Levantine Intermediate Water (LIW) below. We present results of a numerical model investigating the stability of currents in the Strait. The model is nonlinear and uses a hybrid (quasi-isopycnic) vertical coordinate. The model domain is a periodic channel with horizontal dimensions of 400 × 200 km and different bathymetries. As initial conditions, we use seasonal climatological density fields varying only in cross-channel direction. External forcing is not applied. Combining three different bathymetries with both summer and winter climatological data, we show the results of six model integrations. In all cases the flow is baroclinically unstable, the most unstable waves being 100 and 133 km wavelength in summer and 67 km in winter. A cross-channel parabolic bottom profile instead of a flat bottom stabilizes the flow in the north (on the Sicilian side of the Strait) but causes further destabilization in the south (on the African side). Further modification of the bathymetry in terms of shallow shelf sea areas to the south of Sicily leads to a deflection of the summer flow in both the AW and the LIW range and to the generation of stationary eddies. In agreement with observations the final kinetic and eddy kinetic energies of the model are higher in winter than in summer in all model runs. From an inspection of satellite images, evidence was found for unstable waves of similar wavelength as predicted by the model. Records from moored current meters support enhanced flow instability on the African side of the Strait. The position and circulation sense of the stationary eddies in the AW range are found to be consistent with climatology and previously known patches of low sea surface temperature.