The current protocol for detecting and ruling out prostate cancer involves serum PSA testing followed by sampling of the prostate using a transrectal ultrasonography (TRUS)-guided biopsy. Many specialists have discussed how PSA screening has contributed to underdetection of clinically significant prostate cancer, overdiagnosis of clinically insignificant disease and poor risk stratification; however, little consideration has been given to the role of TRUS-guided biopsy in these errors. The performance of TRUS-guided biopsy is constrained by the biomechanical attributes of the sampling strategy, resulting in suboptimal detection efficiency of each core. By using a biomedical engineering approach, a uniform grid sampling strategy could be used to improve the detection efficiency of prostate biopsy. Moreover, the calibration of the sampling can be adjusted by altering the distance between needle deployments. Our model shows that for any given number of needle trajectories, a uniform grid approach will be superior to a divergent, nonuniform strategy for the detection of clinically important disease. This is an important message that should result in a move away from divergent sampling to a uniform grid approach for prostate biopsy.