Abstract: This dissertation compares Trinitarian and Buddhist epistemologies relative to the benchmark of scientific knowledge. To this end, it first develops a methodological framework for this comparison and then derives a comparative benchmark from the post-positivist philosophy of science. The methodological framework is developed by combining Francis Clooney’s comparative theology with Robert John Russell’s method for the Creative Mutual Interaction (CMI) of theology and science. The comparative benchmark is given by the Peircian triadic circuit since this circuit emerges as a methodological invariant within the post-positivist philosophy of science. Trinitarian and Buddhist epistemologies are therefore compared in terms of their respective abilities to ground the Peircian circuit. However, since the Peircian circuit involves a harmonious integration of three distinct operations within a single noetic process, the ability to ground this circuit presupposes a solution to the one-andmany problem. Thus, Trinitarian and Buddhist epistemologies are ultimately compared in terms of their respective approaches to the one-and-many problem. To this end, Theravada, Zen, and Tibetan Buddhist epistemologies are compared with Trinitarian epistemology. These Buddhist Schools have been chosen due to their active participation in the Buddhism-and-science dialogue. Prior to making this each tradition receives a detailed philosophical exposition in which its epistemology is derived from its metaphysical commitment to oneness, manyness, or some combination of the two. Finally, these systems are compared in terms of their respective abilities to solve the one-and-many problem and hence to ground the Peircian circuit. This comparison shows that Trinitarian theology can ground the Peircian circuit because it has a both/and approach to the one-and-many problem and also supports an exhaustive cosmic personalism. By contrast, Theravadin Abhidhamma fails outright because its radical pluralism dissolves the human mind and hence all three Peircian operations. Between these two extremes, Tibetan Madhyamaka and Zen provide a dialectic of oneness and manyness in which the Peircian circuit is neither grounded nor destroyed. For these last two systems, therefore, the Peircian circuit emerges as a de facto structure of conventional knowledge