Prostate-specific antigen (PSA) levels can be transiently elevated in benign conditions. Therefore, guidelines recommend repeat PSA testing before a biopsy. However, PSA should be adjusted for the prostate volume to improve its predictive accuracy for prostate cancer. This study aimed to compare the diagnostic performance of the PSA density and PSA change for prostate cancer and to evaluate whether their combination can further reduce unnecessary biopsies. We retrospectively analyzed patients who underwent a prostate biopsy between January 2020 and December 2024. Inclusion criteria were an initial PSA level between 3 and 20 ng/mL and two PSA measurements within an eight-week interval prior to the biopsy. Patients using 5-alpha reductase inhibitors before the biopsy were excluded. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to compare the diagnostic performance of each predictor for prostate cancer and clinically significant prostate cancer (csPCa). A total of 291 patients were included. Patients with prostate cancer had higher PSA levels, smaller PSA declines, and a higher PSA density. The PSA density showed a superior diagnostic accuracy compared with the PSA change for both prostate cancer and csPCa. The PSA density calculated by a transrectal ultrasound or MRI yielded a similar diagnostic performance. However, the accuracy of the PSA density decreased in patients with a large prostate volume. Incorporating a criterion of a >20% PSA decline to exclude biopsy candidates improved the performance of the PSA density and further reduced unnecessary biopsies. The PSA density demonstrates good diagnostic accuracy for predicting prostate cancer. However, incorporating the PSA change further reduces unnecessary biopsies. Therefore, combining both factors provides a more effective approach for determining the need for a prostate biopsy.