Objectives-Urinary stones are heterogeneous in their fragility to lithotripter shock waves. As a first step in gaining a better understanding of the role of matrix in stone fragility, we measured extractible protein in COM stones that were extensively characterized by micro-computed tomography (micro CT).Methods-Stones were scanned using micro CT (Scanco mCT20, 34 μm), and were ground and protein extracted using four methods: 0.25M EDTA, 2% SDS reducing buffer, 9M urea buffer, and 10% acetic acid. Protein was measured using NanoOrange. SDS extracts were also examined using polyacrylamide electrophoresis (PAGE).Results-Extracted protein was highest with SDS or urea methods (0.28±0.13 and 0.24±0.11%, respectively), and lower using the EDTA method (0.17±0.05%, p<0.02). Acetic acid extracted little protein (0.006±0.002%, p<0.001). Individual stones were significantly different in extractability of protein by the different methods, and SDS-PAGE revealed different protein patterns for individual stones. Extracted protein did not correlate with x-ray lucent void percentage, which ranged from 0.06 to 2.8% of stone volume, nor with apatite content.Conclusions-Extractible stone matrix protein differs for individual COM stones, and yield is dependent on the extraction method used. The presence of x-ray lucent voids or minor amounts of apatite in stones did not correlate with protein content. The amounts of protein recovered were 5 to 10 times lower than that reported by Boyce, showing that these methods extracted only a fraction of the protein bound up in the stones. The results suggest that none of the methods tested will be useful for helping to answer the question of whether matrix content differs among stones of differing fragility to lithotripter shock waves.