Purpose We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort. Materials and Methods This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate specific antigen greater than 4.0 ng/ml or prostate specific antigen less than 4.0 ng/ml but with abnormal digital rectal examination results. The prostate specific antigen measurements were performed in accordance with the standard procedures at the respective institutions. The type of assay used was documented and recalibrated to the WHO standard. Results The incidence of prostate cancer and high grade prostate cancer was lower in the Chinese cohort than the Western cohorts at any given prostate specific antigen level. Around 25% of patients with a prostate specific antigen of 4.0 to 10.0 ng/ml were found to have prostate cancer compared to approximately 40% in U.S. clinical practice. Moreover, the risk curves were generally flatter than those of the Western cohorts, that is risk did not increase as rapidly with higher prostate specific antigen. Conclusions The relationship between prostate specific antigen and prostate cancer risk differs importantly between Chinese and Western populations, with an overall lower risk in the Chinese cohort. Further research should explore whether environmental or genetic differences explain these findings or whether they result from unmeasured differences in screening or benign prostate disease. Caution is required for the implementation of prostate cancer clinical decision rules or prediction models for men in China or other Asian countries with similar genetic and environmental backgrounds.