Introduction: Water vapor intraprostatic injection (Rezum procedure) for benign prostatic hyperplasia (BPH) is one of the most promising minimally invasive surgical treatments. Five-year outcomes from the multicenter randomized controlled trial (RCT) demonstrated significant and durable urinary and sexual function results in selected patients. We compared the sexual and urinary outcomes of this procedure in patients satisfying inclusion criteria of the RCT with unselected patients. Materials and Methods: We prospectively followed all patients with symptomatic BPH who underwent Rezum therapy at eight institutions and analyzed the functional results. Patients were divided into two groups: patients who matched the 5-year RCT inclusion criteria (Group A) and patients who did not (Group B). The pre- and postoperative data, complications, presence of antegrade ejaculation, and urinary and sexual outcomes were periodically recorded. Results: A total of 426 patients were eligible for the study (232 in Group A and 194 in Group B). Patients in Group B had a higher American Society of Anesthesiologists score, prostate volume, and postvoid residual measurement. No difference was found in terms of preoperative International Prostate Symptom Score, International Index of Erectile Function, maximum urinary flow, and prostate-specific antigen. Longer operative time and higher number of vapor injections were required in Group B, with no differences in hospital stay, injection density, and complication rates. All the urinary and sexual outcomes improved with no differences between the two groups. The reintervention rate at the latest follow-up visit was 2.6% in Group A and 3.1% in Group B. Conclusions: In our large multicenter series, water vapor intraprostatic injections showed a safe and effective profile regardless of the prostate size, presence of indwelling catheter, antiplatelet/anticoagulant medications, and patients' comorbidities.

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