The EU Water Framework Directive requires policy to address non-point source pollution as part of an overall integrated strategy to improve the ecological and chemical status of water bodies. Farmers and tax payers would benefit from more cost-effective control measures adequately implemented within watersheds. With this objective, we propose a framework for a spatially-distributed cost-effectiveness analysis of some mitigation measures (buffer strips, longer rotations, mechanical weeding and catch crops) included in agri-environmental programmes of rural development plans. We used the SWAT model to assess the effectiveness of the applied measures and we developed an aggregated bio-economic model using GAMS to evaluate the costs of implementation identifying synergies and trade-offs. Finally, we proposed a ranking of these measures based on their cost-effectiveness ratios and, for each measure, a map of cost-effectiveness ratios by sub basin within the watershed. This approach is applied on the upper stream part of the Gers river basin in the South Western part of France. The findings clearly demonstrated that some measures like grass strips and mechanical weeding could be considered as the most cost-effective measures allowing reduction in pesticides concentration up to 65%. Other measures, such as longer rotation sequences and catch crops, although they appeared less costly to implement, fall short in reducing pollution by pesticides with much higher cost-effective ratios. Possibilities and problems for integrating SWAT model with bio-economic modeling with spatial and temporal scale issues are discussed along with the use of this integrated framework as communication tools in participatory river basin management.