A study was conducted on a large-scale irrigated area located in southern Italy to analyze the cumulative effects of long-term water management practices on soils and aquifers. Assessing the environmental sustainability of irrigation systems operations was the main goal of the present research. This included envisaging feasible changes to business-as-usual in the study area with the aim of reducing pressures and of meeting current and future management objectives. The Determinants-Pressure-State-Impact-Response methodology suggested by the European Environmental Agency was applied to the case study to analyze cause-effect relationships between driving forces, pressures and potential impacts. Simulations of alternatives in water management and evaluation of resulting consequences were conducted by developing a spatial Decision Support System (DSS) on the study area. This basically involved development and ranking of alternatives by using a commercial software package (DEFINITE DSS). Evaluation of the most likely resulting consequences was conducted by creating maps of environmental risk by means of two commercial GIS software packages (ArcGIS and IDRISI). The used approach showed its usefulness for achieving better understanding of relevant aspects related to management of irrigation water at regional scale, for designing strategic monitoring programs to be implemented and for envisaging feasible management alternatives on large-scale irrigation systems.