The purpose of this article is to discuss the conceptual framework and strategies used in theory-driven evaluations in relation to mixed methods research and to explore the opportunities and challenges emerging from theory–driven applications. Theory-driven evaluations have frequently applied mixed methods in the past, and these experiences provide some insightful information for future development of mixed methods. In theory-driven evaluations, the application of mixed methods is justified and applied under a conceptual framework called program theory. The conceptual framework of program theory provides a plan and agenda for mixed methods to work collaboratively and de-emphasizes their differences and incompatibilities. Based upon the conceptual framework of program theory, this article provides several strategies for combining qualitative and quantitative methods in theory-driven evaluations. Procedures in applying these strategies are systematically illustrated. Finally, this article discusses challenging issues related to the future development of mixed methods, such as implications of the use of pure versus modified forms of mixed methods and the advocacy of mixed methods research as a “method” paradigm versus a “method use” paradigm