Purpose: This prospective, multicenter study was initiated to evaluate the diagnostic performance of PSA, free/total PSA (f/tPSA) and complexed PSA (cPSA) with volume-based parameters for early detection of prostate cancer in patients with PSA between 2.5 and 20 ng/ml. Materials and Methods: 408 subjects with serum PSA values between 2.5 and 20 ng/ml regardless of digital rectal examination (DRE) were included in to the study. The diagnostic validity, sensitivity, specificity and cut-off values were evaluated by Receiver Operating Characteristic (ROC) curve analysis. Results: Of 408 patients 77 (18.9%) were positive for prostate cancer. Digital rectal examination was non-suspicious in 86% (351/408) of the patients. Area under curve (AUC) values for cPSA were better than PSA and f/tPSA in patients with PSA values of 2.5-10 ng/ml and 4-10 ng/ml, as well as the whole group. Furthermore, on ROC curve analysis cPSAD was the best predictor of prostate cancer for all PSA ranges regardless of the DRE findings except PSA values between 2.5 and 4 ng/ml. The cut-off value of cPSAD at 90% sensitivity was 0.06 ng/ml/cm3 with a 35.3% specificity saving 126 unnecessary biopsies in the whole group. Conclusion: cPSA might be a better initial test than PSA for prostate cancer detection and measurement of cPSA alone and its derivatives obviate the need for additional fPSA testing. © 2004 Elsevier B.V. All rights reserved.