During the early 2000s, the Environmental Protection Agency's (EPA's) Office of Research and Development, Global Change Research Program, supported three watershed assessments to evaluate different approaches and tools for understanding and managing climate and land-use change impacts on watershed ecological resources. Watershed assessments were conducted for (1) several small rivers in southern Maryland, (2) Arizona's San Pedro River, and (3) California's Sacramento River. In this report, we comparatively analyze the three case-study approaches in order to develop recommendations that may be useful as guidance to others conducting similar assessments. Key insights gained from these studies include: (1) Prioritize locations for studies to maximize decision support. (2) Target selection of stakeholders, establish credibility of underlying methods and models, and incorporate incentives for mutually beneficial results. (3) Provide essential climate science capabilities and tools to project teams. (4) Develop model linkages at the onset, carry out assessment activities at multiple scales, and require explicit uncertainty analysis of results. The watershed assessment case studies described in this report yield richness of detail in terms of methods and results, as well as inform more generally on best practices for conducting future watershed assessments. However these were pioneering studies addressing difficult and complex problems.