Objective: To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate (ThuFLEP) in the treatment of oversized (>200 mL) prostate. Methods: Clinical data of 475 benign prostatic hyperplasia (BPH) patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed, all of whom were treated with thulium fiber laser, and the patients were divided into three groups according to the total volume of the prostate (TPV): group A (TPV < 100 mL), group B (100 mL≤TPV < 200 mL), and group C (TPV≥200 mL). The age of the patients in the three groups [(69.38±7.79) years, (69.64±8.69) years, (70.32±7.44) years], International Prostate Symptom Score (IPSS) [(22.7±1.9), (22.8±2.7), (25.8±3.7)], and the maximum urinary flow rate (Qmax) [(7.9±2.7) mL/s, (9.3±4.3) mL/s, (9.9±3.3) mL/s] were not statistically significant (P>0.05). The prostate volume in the three groups [(103.49±46.19) mL, (75.73±30.69) mL, (273.49±49.19) mL] and prostate specific antigen (PSA) [3.52 (1.05, 8.76) μg/L, 6.78 (1.61, 7.45) μg/L, 8.52 (5.05, 12.76) μg/L] were statistically significant (P < 0.05). Results: All surgeries were successfully completed. The dif-ferences in enucleation time [30.0 (21.2, 44.5) min, 41.6 (31.2, 52.5) min, 45.1 (35.2, 50.0) min] and hospitalization time [(6.06±1.21) d, (6.15±1.50) d, (7.71±1.74) d] among the three groups were not statistically significant (P>0.05); and the differences in the postoperative indwelling catheter time [(4.0±1.4) d, (4.0±1.3) d, (6.6±1.1) d], operative time [61 (42, 89) min, 82 (62, 105) min, 115 (96, 142) min], enucleation efficiency [1.29 (0.71, 1.56) g/min, 1.67 (1.23, 2.15) g/min, 2.74 (2.20, 3.34) g/min], and hemoglobin drop values [12 (7, 19) g/L, 17 (11, 24) g/L, 27 (19, 35) g/L] were statistically different (P < 0.05). Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight (r=0.880, P < 0.001), and the enucleation efficiency increased with the increase of prostate volume. The differences in IPSS [(6.6±1.7), (6.2±1.4), (4.6±1.1)] and Qmax [(18.9±3.1) mL/s, (16.8±3.8) mL/s, (22.9±7.1) mL/s] were not statistically significant among the three groups (P>0.05), and the differences in IPSS and Qmax were statistically significant compared with those before surgery. The differences were statistically significant in preoperative comparisons, but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax (P < 0.05). The patients in the three groups were followed up for 3 months, and post-operative complications were categorized into Clavien-Dindo Ⅰ (urinary retention, persistent hematu-ria), Clavien-Dindo Ⅱ (glandular remnants, urinary tract infection, blood transfusion) and Clavien-Dindo Ⅲ (urethral stenosis, contracture of the bladder neck, and reoperation for hemorrhage) based on the Clavien-Dindo Complications System score, the incidence of Clavien-Dindo in the three groups was 5.2% (13 cases), 6.7% (12 cases) and 12.1% (7 cases), respectively, with statistically significant differences (P < 0.05); among them, there were statistically significant differences in urinary infection, blood transfusion and bleeding reoperation (P < 0.05), and there was no statistically significant difference in the remaining complications (P>0.05). Conclusion: The risk of blood transfusion and re-hemostasis increases with larger prostate volume, the efficiency of enucleation increases with the increase of prostate vo-lume, and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.