The Health Impact Assessment (HIA) is a procedure with the aim to protect the populations exposed to the impacts deriving from the establishment or upgrading of large industrial enterprises, i.e. large combustion plants (>300 MWth). In Italy a guideline for the HIA procedure has been published in compliance with the 2014/52/EU Directive on the Environmental Impact Assessment (EIA) requirements. Italian HIA procedure. An ecotoxicological approach has been included for the first time in the HIA procedure with the aim to detect toxic effects caused by unknown not-monitored contaminants or mixtures in the ecosystem components affected by the potential emissions, discharges and releases of large industrial enterprises. Ecotoxicology plays an important bridge role between environment and human health in the scoping and monitoring step of the HIA procedure with a key function of early warning system and screening. The aim of this paper is to present the Italian experience in the first three years of the application of the new approach, proposing recommendations on specific case studies. Conclusion and future perspective. 80% of enterprises, that applied HIA, have delivered a robust, integrated and detailed documentation in relation to the ecotoxicological assessment, this positive feedback will generate environmental and human health benefits to the areas where the plants are established.