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We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record.We defined sample cohorts of men with prostate cancer using data from the Veterans Health Administration, including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using prostate specific antigen values from the Veteran Affairs Central Cancer Registry vs the gold standard electronic health record laboratory file results.There was limited agreement among cohorts when defined by cancer registry prostate specific antigen values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with prostate specific antigen less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with prostate specific antigen between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry prostate specific antigen value had significantly different overall survival when compared with patients assigned based on registry and laboratory file prostate specific antigen values.Cohorts based exclusively on cancer registry prostate specific antigen values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes.