Background: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening. Methods: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42 376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs. Results: Mean lead times and rates of overdetection depended on a man’s age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6–14.1 years) and the overdetection rate was 27% (range = 24%–37%); at age 75, the estimates were 6.0 years (range = 5.8–6.3 years) and 56% (range = 53%–61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8–12.1 years), and the overdetection rate was 48% (range = 44%–55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%–87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%–57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%–116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected. Conclusions: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year.