Tumor-associated macrophages (TAMs) are highly active immune effector cells that may either positively or negatively regulate the growth of various malignant cells, depending on the biological context. However,the role of TAMs in human prostate cancer progression is unclear. TAMs were immunohistochemically labeled using a monoclonal (CD68) antibody in radical prostatectomy specimens derived from 81 prostate cancer patients. CD68-positive cells were counted with the aid of a microscope and expressed as macrophage index (M_φI), including TAMs/mm² total tumor tissue(M_φI_total),TAMs/mm² tumor stroma(M_φI_stroma),and TAMs/mm² cancer cell area(M_φI_cancer). M_φIs were analyzed in association with patients’clinical and pathological stage, recurrence status, and histological grade of the cancer. There were significant inverse relationships between M_φI_totaland M_φI_stromaand clinical stage (P = 0.016 and P = 0.006, respectively). Reduced M_φI_totalwas also associated with the presence of positive lymph nodes(P = 0.010). Interestingly, although all of the M_φIs differed between Gleason score groups, only M_φI_cancerwas positively associated with Gleason score. Univariate analysis of M_φI_totaland multivariate analysis of M_φI_totalwith specific pathological markers revealed that M_φI_totalwas an independent predictor for disease-free survival after surgery(Cox proportional hazard model, P = 0.044 and P = 0.007, respectively). For patients with high M_φI_total(≥185.8, the mean M_φI_totalvalue), the disease-free probability 5 years after surgery was 0.75,which was significantly higher than for those with low M_φI_total(0.31, P = 0.0008). Additional immunohistochemical studies that evaluated cytotoxicity-related biomarkers in stroma-associated mononuclear cells suggested reduced functional activities in highly aggressive prostate cancer compared with less aggressive disease. Our results indicate that reduced M_φI_totalis a novel prognostic marker for prostate cancer.