Objectives: To determine the operating characteristics of prostate-specific antigen (PSA) testing and prostate cancer diagnosis rates in men who have had an initial PSA test in Tayside. Setting: A retrospective cohort study in Tayside, Scotland from 1992 to 2001. Methods: In total, 20,623 men were PSA tested during the period 1992-2001. After exclusions, 19,660 were studied. Sensitivity and specificity were calculated for various PSA cut-off values by age group using logistic regression weighted for verification bias (biopsy). Cox regression analysis was performed using six test pattern cohorts. Results: The annual rate of PSA testing increased from 5.1 per 1000 man years in 1992 to 21.3 per 1000 man years in 2001. The average number of PSA tests per patient increased from 1.11 in 1992 to 2.57 in 2001. Prostate cancer diagnosis and death rates remained constant from 1995 onward. The PSA test had generally inadequate sensitivity and specificity values, so a unique cut-off could not be found for the two older age groups which could be used as a recommendation for biopsy. The commonly used 4 ng/mL cut-off was reasonably sensitive and specific only for the under 60 age group with values of 92.4% and 90.7%, respectively. For prostate cancer diagnosis, the hazard ratios (HR) were reported relative to those with a series of all normal tests. For those with an initially normal PSA test who had at least one abnormal retest result the HR for diagnosis was 10.43 (95% confidence interval [CI] 6.17-17.63). For those with initially abnormal tests with normal retests HR = 1.63 (95% CI 0.65-4.07). Conclusions: There are no optimal PSA cut-off values for older age groups with which to make a confident referral for biopsy. The increase in PSA testing and the questionable cut-off values of the test calls for the development of an alternative screening strategy.