Scientific research is complex, and it must be replicated. Replication and accuracy require significant economic resources. This chapter presents and appraises C. S. Peirce’s theory of an economics of research project selection and replication as part of a larger concern for increasing the reliability and integrity of scientific research. Peirce’s conception of the economy of research has been employed by philosopher Nicholas Rescher to interpret and constructively criticize Popper’s notion of falsification in appraising theories. Peirce was a remarkable post-Civil War figure and one of the prominent co-founders of American pragmatism in philosophy. Peirce’s proposal for an economic approach to science may be seen as inaugurating an economic approach to science. Peirce’s conception of the economy of scientific research extended beyond a concern for enhancing the accuracy of measurements and results with repeated experiments or alternatively designed instruments.