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The introduction of renewable alcohols as fuels for heavy-duty engines may play a relevant role for the reduction of the carbon footprint of the transport sector. The direct injection of ethanol as main fuel and diesel as pilot fuel in the engine combustion chamber through two separate injectors may allow good combustion controllability over the entire engine operating range by targeting diffusive combustion. Closed-cycle combustion simulations have been carried out using AVL FIRE coupled to AVL TABKIN for the implementation of the Flamelet Generated Manifold (FGM) chemistry reduction technique in order to investigate the influence of the injection system geometry and the injection strategy of pure ethanol and diesel fuel on ignition characteristics and combustion at different operating conditions.