Objective: Lutetium-177 prostate-specific membrane antigen-617 is a novel alternative therapeutic option in metastatic castration-resistant prostate cancer, especially useful for patients who do not respond to standard therapy methods. The aim of this study was to define the efficacy and safety profile of lutetium-177 prostate specific membrane antigen-617 treatment in a group of patients with metastatic castration-resistant prostate cancer. Materials and Methods: Study group included 34 men with metastatic castration-resistant prostate cancer (median, 69.6 ± 7.7 years) who were treated with lutetium-177 prostate-specific membrane antigen-617 therapy (22/34; 4 courses, 12/34; 2 courses). Patients were evaluated by physical examination, Eastern coop erative oncology group performance status, gallium-68 prostate-specific membrane antigen positron emis sion tomography/computed tomography, brief pain inventory-short form questionnaire, biochemical tests, and complete blood counts. Treatment response and adverse effects were examined by brief pain inventory scores, SUVmax values, biochemical tests, and complete blood counts. Independent variables were analyzed statistically (significance; P < .05). Results: The Eastern cooperative oncology group performance was grade 0 in 5/34 (14.7%), grade 1 in 25/34 (73.5%), and grade 2 in 4/34 (11.8%) patients. Distribution of patient numbers according to brief pain inven tory scores (score: <1, scores: 1-4, and scores: 5-10) was 2, 10 and 22 at the beginning, 6, 16 and 12 after the second course, and 10, 10 and 2 after the fourth course of treatment, respectively. Serum prostate-specific antigen decreased in 15 of 22 patients (68%) (P < .05). Before and after the treatment, we found a substan tial decrease in SUVmax values (22.3 vs. 11.8, P < .001) and brief pain inventory scores (score ≥ 5; 22/34 pts vs. 0/22 pts). The counts of white blood cells (P < .05), hemoglobin (P < .05), and thrombocytes (P=.001) were all significantly lower at the conclusion of the therapy. The most important adverse events were severe leukopenia (1/34 pts; 2.29 × 103 /µL) and thrombocytopenia (3/34 pts; 32 000, 36 000, 32 000 × 106 /L). Conclusion: We found that lutetium-177 prostate-specific membrane antigen-617 therapy is a promising treatment method for metastatic castration-resistant prostate cancer patients who are unresponsive to conventional therapy, according to our biochemical, positron emission tomography/computed tomography, and pain score outcomes.