Background: The value of digital rectal examination (DRE) as a screening test for prostate cancer (PC) is controversial in the current prostate-specific antigen (PSA) era. Objectives: To determine (1) the additional value of a suspicious DRE for the detection of PC in men with an elevated PSA level in subsequent screenings and (2) the tumour characteristics of PCs detected in men with a suspicious DRE. Design, setting, participants: Within the screening study, from 1997-2006 men aged 55-75 years were invited for an every 4-yr PSA determination. A PSA level > 3.0 ng/ml prompted a DRE and a transrectal ultrasound (TRUS)-guided, lateralized sextant biopsy. Throughout the three screenings of the ERSPC, Rotterdam, 5040 biopsy sessions were evaluated. Measurements: We deter-mined the positive predictive values (PPVs) of a suspicious DRE and normal DRE, which entailed, respectively, the proportion of PCs detected in men with a suspicious DRE or normal DRE divided by, respectively, all biopsied men with a suspicious DRE or normal DRE. Results and limitations: At initial screening, the PPV of a suspicious DRE, in conjunction with an elevated PSA level, to detect PC was 48.6% compared to 22.4% for men with a normal DRE. Both PPVs decreased in consecutive screens: respectively, 29.9% versus 17.1% (screen 2) and 21.2% versus 18.2% (screen 3). Respectively, 71.0% (p < 0.001), 68.8% (p < 0.001), and 85.7% (p = 0.002) of all PCs with a Gleason score > 7 were detected in men with a suspicious DRE at screens 1, 2, and 3. A limitation is that only biopsied men were evaluated. Conclusions: At initial and subsequent screenings, the chance of having cancer at biopsy was higher in men with a suspicious DRE compared to men with a normal DRE (to a lesser extent in subsequent screenings), and the combination of a PSA level > 3.0 ng/ml with a suspicious DRE resulted in detecting significantly more PCs with Gleason score > 7. DRE may be useful in more selective screening procedures to decrease unnecessary biopsies and overdiagnosis. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.