PURPOSE: Liquid biopsies with circulating tumor DNA (ctDNA) analysis are increasingly being utilized as a non-invasive approach to identify actionable genomic alterations in advanced/metastatic cancers. Herein, we report the correlation between ctDNA analysis of plasma samples collected from patients enrolled in the NCI-MATCH trial and tumor tissue-based sequencing. PATIENTS AND METHODS: We analyzed plasma samples collected from patients enrolled on 16 subprotocols of NCI-MATCH who had plasma samples collected within 90 days before starting treatment. Concordance was defined as the detection of the same gene alteration leading to patient enrollment in NCI-MATCH in both tissue and plasma. RESULTS: We included 300 patients who were enrolled in NCI-MATCH. Most patients (81%, n=243) were enrolled based on central tissue testing and had contemporaneous tissue and plasma samples. The tissue alteration of interest was detected in the plasma of 81.1% (n=197) of patients. Lower rates of detection of the tissue alteration of interest were observed in samples from 57 patients who were enrolled based on outside designated laboratory testing (56.1%, n=32) and had non-contemporaneous tissue and plasma samples. Variations in concordance rates were observed with different alteration types, by maximum plasma variant allelic frequency, and based on tumor biopsy site. CONCLUSIONS: The tumor tissue alteration of interest was detected in the plasma of 81% of patients who were enrolled in the NCI-MATCH trial based on central tissue testing and had contemporaneous tissue and plasma samples. This suggests a potential role for liquid biopsy in patients' enrollment in trials evaluating biomarker-driven anticancer therapies.