Introduction: Prostate-specific antigen velocity (PSAV) is used to monitor men with clinical suspicion of prostate cancer (PCa), with a normal cut-off point of 0.3–0.5 ng/mL/year. The aim of the study is to establish the predictive capacity of PSAV (value and acceleration) and of the free PSA/total PSA index or ratio. Method: Prospective multicentre observational study in 2035 men of over 47 years of age. Inclusion criteria: men who wished to be informed on the health of their prostate. Exclusion criteria: men with a previously diagnosed prostate condition. Groups: GA: (n = 518): men with serum PSA equal to or greater than 2.01 ng/mL. GB: (n = 775): men with serum PSA greater than or equal to 0.78 ng/mL and less than 2.01 ng/mL. GC: (n = 742): men with serum PSA less than 0.78 ng/mL. Variables: prostate-specific antigen (PSA); age; body mass index (BMI); PSA velocity (PSAV) (ng/mL per year); free PSA/total PSA index (iPSA); PSAV acceleration (increasing: positive, or decreasing: negative); prostate diagnosis (benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), or infectious and non-infectious prostatitis and prostatic adenocarcinoma (PCa)); de novo diagnoses of urinary tract diseases or conditions; concomitant treatments, diseases and conditions; final diagnosis of prostate health. Results: Mean age 62.35 years (SD 8.12), median 61 (47–94); age was lowest in GC. Mean BMI was 27.89 kg/m2 (SD 3.96), median 27.58 (18.56–57.13); no differences between groups. Mean PSAV was 0.69, SD 2.16, median 0.13 (0.001–34.46); PSAV was lowest in GC. Mean iPSA was 27.39 u/L (SD 14.25), median 24.29 (3.7–115); iPSA was lowest in GA. PSAV had more positive acceleration in GA and more negative acceleration in GC. There were 1600 (78.62%) cases of normal prostate or BPH, 322 (15.82%) cases of PIN or non-infectious prostatitis, and 113 (5.55%) cases of PCa. There were more cases of BPH in GC and more cases of PIN or prostatitis and cancer in GA (p = 0.00001). De novo diagnoses: 15 cases of urinary incontinence (UI), 16 discomfort/pain in LUT, 112 cases of voiding disorders, 12 urethral strictures, 19 hematuria, 51 cystitis, 3 pyelonephritis, 4 pelvic inflammatory disease; no differences were found between groups. In the multivariate analysis, PSAV and the direction of PSAV acceleration (positive or negative) were the variables which were correlated most strongly with prostate health. iPSA was associated with the presence of prostatitis, PCa, and BPH. Men in GA had more prostatitis, PCa, treatment with alpha blockers, and history of previous smoking. GB had more cases of BPH and more positive acceleration of PSAV. GC had more normal prostates, more BPH, more use of ranitidine, and more PSAV with negative acceleration. Conclusions: PSAV, direction of PSAV acceleration, and iPSA in PSA cut-off points of 0.78 ng/mL and 2.01 ng/mL in a priori healthy men over 47 predict the probability of benign or malignant pathology of the prostate.