Routine screening for prostate cancer remains controversial. However, it is very important to show how the optimal rescreening interval should be set for men who want to be screened after informed consent. To solve this issue, the risk of prostate-specific antigen (PSA) increase above 4.0 ng/ml relative to baseline PSA levels and age was investigated. Between 1988 and 2000, 7,757 subjects screened twice or more and also with baseline PSA levels of 4.0 ng/ml or lower were enrolled in our study. All serum PSA levels were measured by E-test Tosoh II PA assay at one center. Interval PSA levels for men undergoing screening with a greater than 1 year interval were calculated on the assumption that PSA levels changed over time in a simple exponential fashion. Then, the cumulative rate of freedom from PSA increase above 4.0 ng/ml was estimated using the Kaplan-Meier technique stratified by baseline PSA ranges of 0.0 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 ng/ml and every 10 years of age ranges. Of the 7,757 subjects, 559 (7.2%) were expected to have had PSA levels increase above 4.0 ng/ml within 5 years after the baseline PSA measurements. The cumulative rate of freedom from the PSA increase above 4.0 ng/ml at 5 years was 98.7%, 92.9%, 70.3% and 38.5% in cases of baseline PSA levels of 1.0 ng/ml or lower, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively. The cumulative rates of freedom from the PSA increase were significantly decreased with the baseline PSA ranges being higher regardless of age range. Re-screening interval should be set stratified by baseline PSA levels, regardless of age and race. Rescreening interval should be set at 1, 1 to 2 and 3 to 5 years for men with baseline PSA ranges of 2.1 to 4.0 ng/ml, 1.1 to 2.0 ng/ml and 0.0 to 1.0 ng/ml, respectively, in individual-based screening. In mass screening system using PSA alone, rescreening interval should be set in the same manner as in individual-based screening, except for men with baseline PSA levels of 1.1 to 2.0 ng/ml, which should be set at 1 year to avoid developing incurable prostate cancer. © 2004 Wiley-Liss, Inc.