AbstractEarly diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of faecal protein biomarkers for the detection of colorectal neoplasms with consideration of a wide range of covariates. A systematic literature search was performed up to Jun 10, 2021 on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined to be clinically applicable (CA) if they had areas under the curve > 0.70 and positive and negative likelihood ratios > 2 and < 0.5, respectively. A total of 47,059 test results were extracted from 16 immunochemical faecal occult blood test (iFOBT), 26 pyruvate kinase-M2 (PK-M2) and 23 faecal calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P = 0.02 versus PK-M2 and P < 0.01 versus FC for CRC; P < 0.01 versus PK-M2 for AN). Regarding covariates, the lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to the enzyme-linked immunosorbent assay (P < 0.01). iFOBT is recommended as the most accurate faecal biomarker for CRC and AN diagnosis.