By examining the long-term outcomes of males with negative transrectal ultrasound (TRUS) biopsy results who did not get MRI, 1 can investigate the oncologic risk of such malignancies. The goal was to analyze mortality following the first and second negative TRUS biopsies. All men who had initial TRUS biopsies were included between January 1, 1995, and December 31, 2016. A total of 6,389 men underwent a re-biopsy, and 37,214 men had a negative result from the initial TRUS biopsy. With competing risks, the risk of cause-specific death was examined. Prostate-specific antigen (PSA), age, and digital rectal examination were all considered in a multivariable logistic regression analysis of the diagnosis of Gleason grade more than equal to 7 prostate cancer after negative biopsies. Prostate cancer-specific mortality over 15 years was 1.9% (95% [CI]: 1.7-2.1). For males with PSA levels of less than 10 and more than 20 ng/ml, respectively, the prostate cancer-specific death rate was 1.3% (95% [CI]: 0.9-1.6) and 4.6% (CI]: 3.4-5.8. About 12% of the TRUS re-biopsies had Gleason scores less than equal to 7, and the chance of Gleason scores less than equal to 7 increased with longer re-biopsy times (P<0.001). Similar to the original biopsy, mortality followed a second biopsy. When their PSA is below 10 ng/ml, men with negative TRUS biopsies had very low prostate cancer-specific mortality rates. It is recommended that MRI targeting should only be advised for men with PSA more than 10 ng/ml following a negative biopsy. It raises major concerns about the routine use of MRI targeting for initial prostate biopsy.