The American Cancer Society estimates that in 2011, about 241,000 men will be diagnosed with prostate cancer and 34,000 men will die from it, making it the most commonly diagnosed nonskin cancer and the second leading cause of cancer death in men. Prostate-specific antigen (PSA)-based screening programs have been advocated as a possible means to reduce the mortality rate, as the test can detect asymptomatic, early-stage tumors. Beginning in the 1990s, utilization of the PSA test became widespread in U.S. clinical practice; data from nationally representative surveys and community primary care clinics consistently show that the majority of American men aged 50 years and older receive regular PSA tests. This evidence update summarizes new and previously reviewed randomized controlled trials, systematic reviews, and meta-analyses to answer the following key questions: 1) Does PSA-based screening decrease prostate cancer-specific or all-cause mortality? and 2) What are the harms of PSA-based screening for prostate cancer? "PSA-based screening" is defined as a screening program for prostate cancer in asymptomatic men that incorporates one or more PSA measurements, with or without additional modalities such as digital rectal examination or transrectal ultrasonography. "Asymptomatic" is defined as without symptoms that are highly suspicious for prostate cancer. Many older men have chronic, stable lower urinary tract symptoms (e.g., due to benign prostatic hyperplasia ) that are not generally associated with an increased risk for prostate cancer. As in a previous review for the USPSTF, a broad definition of PSA-based screening was utilized that includes traditional single-threshold PSA testing as well as other PSA-based prognostic measures, such as age-adjusted thresholds, velocity, and doubling time.