To assess the diagnostic efficacy of prostate-specific antigen (PSA)-related parameters, using a total of 226 patients with gray zone PSA who underwent prostate biopsy, various cutoff points of free to total ratio of PSA (f/t PSA) and PSA velocity (PSAV) were evaluated. Higher cutoff points of f/t PSA resulted in high sensitivity and negative predictive value (NPV): at f/t PSA <15%, sensitivity was 82.0% (41/50) and NPV 84.7% (50/59), and at f/t PSA <20%, 96.0% (48/50) and 92.3% (24/26). Lowering cutoff points also resulted in higher sensitivity and NPV: at PSAV >or=0.75 ng/ml per year, sensitivity was 71.4% (15/21) and NPV 82.4% (28/34), and at PSAV >or=0.40 ng/ml per year, 95.2% (20/21) and 95.2% (20/21). Further, among the patients with both of these parameters available, both sensitivity and NPV achieved 100% (10/10 and 7/7) when the indication for biopsy was determined as f/t PSA <15% or PSAV >or=0.40 ng/ml per year. Our results showed that unnecessary prostate biopsies could be more effectively avoided among patients with "gray zone PSA" by combination of f/t PSA and PSAV than single usage of these indexes.