Objective: To evaluate the levels of angiogenesis-related biomarkers, including Thrombospondin-1 (TSP1), Endostatin, Osteopontin, and Tumstatin, in prostate cancer patients and their relationship with tumor spread and clinical parameters. Methods: This prospective study included 92 participants divided into three groups: 33 prostate cancer patients, 29 patients with benign prostatic hyperplasia (BPH), and 30 healthy controls. Biomarker levels were analyzed and compared among the groups. Results: Osteopontin levels were significantly higher in the prostate cancer group (108.5 ng/mL) compared to the BPH (66.02 ng/mL) and control groups (56.5 ng/mL). TSP1 levels were lower in prostate cancer group (16.3 ng/mL) than in the BPH (25.3 ng/mL) and control groups (21.5 ng/mL). Similarly, Endostatin levels were reduced in the prostate cancer group (146.3 ng/mL) compared to the BPH (163.3 ng/mL) and control groups (166.2 ng/mL). No significant differences in Tumstatin levels were observed among the groups. Conclusions: Elevated Osteopontin levels correlate with higher Gleason scores and metastatic potential, while lower TSP1 and Endostatin levels are associated with advanced tumor progression. These biomarkers may serve as indicators of prognosis in prostate cancer, though larger studies are required for validation.