We investigated the use of a new type of FOBT (EZ-Detect) that uses the blood's pseudo-peroxidase activity as an enzymatic catalyst, in a one-step chromogen-substrate system performed by the patient. Asymptomatic patients >/=50 years old received three Hemoccult II (HO) cards and three EZ-Detect (EZ) packages to be used in three consecutive bowel movements. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of colorectal neoplasia was calculated. The study included 207 patients, with a mean age of 58.9 years. Diagnostic accuracy for detection of adenomas was similar for the EZ and HO tests (66.7% vs. 71.0%; P=0.48), while for advanced adenomas diagnostic accuracy for the EZ and HO tests was 86.0% vs. 94.2% (P=0.01), respectively. Most patients preferred the EZ test (92% vs. 8%). We conclude that the EZ test has a diagnostic profile similar to that of the HO test for identification of adenomas; however, for advanced adenomas the diagnostic accuracy was slightly better for the HO. The EZ test was preferred by most patients, which may increase colorectal cancer screening compliance.