The presence of ascites in peritoneal metastases (PM) portends a poor prognosis for all intra-abdominal malignancies. However, the molecular ligands within ascites and their biological relevance remain unclear. We report a comprehensive proteomics analysis of cell-free ascites in PM, including 160 malignant PM ascites covering a spectrum of 17 histological origins and 15 ascites of benign origin. This is the first large-scale proteomic analysis of cell-free ascites across diverse histological subsets of PM that can be harnessed for discovery of novel therapeutics and understanding of PM biology.