Increasing water scarcity challenges conventional approaches to managing water resources. More holistic tools and methods are required to support the integrated planning and management of fresh water resources at the river basin level. This paper compares an index-based cost-effectiveness analysis (IBCEA) with a least-cost river basin optimization model (LCRBOM). Both methods are applied to a real case study to design a cost-effective portfolio of water demand and supply management measures that ensures compliance with water supply and environmental targets. The IBCEA is a common approach to select programmes of measures in the implementation of the EU Water Framework Directive. We describe its limitations in finding a least-cost solution at the river basin level and highlight the benefits from implementing a LCRBOM. Both methods are compared in a real case study, the Orb river basin, in the south of France. The performances of the programmes of measures selected by the two methods are compared for the same annual equivalent cost. By ignoring the spatial and temporal variability of water availability and water demands in the river basin and the interconnection among its elements, the aggregated approach used in the standard IBCEA can miss more cost-effective solutions at the river basin scale. ; University Lecturer Training Programme (FPU12/03803) of the Ministry of Education, Culture and Sports of Spain ; IMPADAPT project /CGL2013-48424-C2-1-R) from the Spanish ministry MINECO (Ministerio de Economía y Competitividad) and European FEDER funds ; Conseil Régional du Languedoc Roussillon et ONEMA ; Conseil Général de l’Hérault ; Agence de l’Eau Rhône Méditeranée et Corse ; Girard-Martin, CDP.; Rinaudo, J.; Pulido-Velazquez, M. (2015). Index-Based Cost-Effectiveness Analysis vs. Least-Cost River Basin Optimization Model: Comparison in the Selection of a Programme of Measures at the River Basin Scale. Water Resources Management. 29:4129-4155. doi:10.1007/s11269-015-1049-0. ; Senia ; 4129 ; 4155 ; 29