Abstract Introduction Rezum therapy demonstrates efficacy for benign prostatic hyperplasia (BPH), but outcomes in large prostates remain unclear. Objective To evaluate Rezum efficacy in large prostates, assess success rates, and identify predictors of treatment outcomes. Methods Retrospective analysis of 597 patients undergoing Rezum therapy (2019-2023). We identified 133 patients with large prostates receiving ≥8 steam treatments and a minimum 3-month follow-up. Outcomes included symptom scores (IPSS, IPSS-QoL), uroflowmetry (Q-max), post-void residual (PVR), sexual function, and retreatment rates. Multivariable regression identified predictors of treatment failure. Results Among 133 patients with complete follow-up, sexual function preservation was a primary concern for 112 patients, while 21 patients had ASA class 3 comorbidities. 19 of 21patients received local anesthesia, and 2 patients received brief general anesthesia. At three-month follow-up, sexual function outcomes were favorable: 96.2% (107/112) of patients reported no change in erectile function, with 4 patients reporting deterioration and 1 reporting improvement. Regarding ejaculatory function, 94.6% (106/112) reported no changes, 3 patients reported improvement, 2 patients experienced decreased semen volume, and 1 patient developed anejaculation. Significant improvements in urinary symptoms were observed at three months. Median IPSS decreased from 23 (IQR: 18-26) preoperatively to 9 (IQR: 5-13) postoperatively (P<0.001). Similarly, median IPSS-QoL scores improved from 4 (IQR: 4-5) to 2 (IQR: 1-3) (P<0.001). Objective uroflowmetry parameters also showed substantial improvement: median Q-max increased from 8 mL/s (IQR: 5.6-11) to 13 mL/s (IQR: 9.6-16.5) (P<0.001), while median post-void residual volume decreased from 155 mL (IQR: 65-291) to 57 mL (IQR: 27-121) (P<0.001). During a median follow-up period of 27 months (IQR: 12-47), 20.3%(27/133) of patients required retreatment, with a median time to retreatment of 18 months (IQR: 31-48). Multivariable analysis identified significant predictors of treatment outcomes: larger prostate size was associated with higher odds of treatment failure (OR = 0.963, 95% CI: 0.936-0.990, P=0.009), while better Q-max at three-month follow-up was predictive of sustained treatment success (OR = 1.27, 95% CI: 1.1-1.83, P=0.045). Conclusions Rezum therapy is effective for large prostates with excellent sexual function preservation. However, larger prostate size increases retreatment risk. Early Q-max improvement could be predicting long-term success treatment. Disclosure No