In this paper, we present an architecture and a formal framework to be used for systematic benchmarking of monitoring and diagnostic systems and for producing comparable performance assessments of different diagnostic technologies. The framework defines a number of standardized specifications, which include a fault catalog, a library of modular test scenarios, and a common protocol for gathering and processing diagnostic data. At the center of the framework are 13 benchmarking metric definitions. The calculation of metrics is illustrated on a probabilistic model-based diagnosis algorithm utilizing Bayesian reasoning techniques. The diagnosed system is a real-world electrical power system, namely the Advanced Diagnostics and Prognostics Testbed (ADAPT) developed and located at the NASA Ames Research Center. The proposed benchmarking approach shows how to generate realistic diagnostic data sets for large-scale, complex engineering systems, and how the generated experimental data can be used to enable “apples to apples” assessments of the effectiveness of different diagnostic and monitoring algorithms.