Introduction: To present the initial report of single-port transvesical enucleation of the prostate in 3 patients with large-volume benign prostatic hyperplasia. Methods: Single-port transvesical enucleation of the prostate was performed in 3 patients with large-volume (187, 93, and 92 g) benign prostatic hyperplasia. A novel single-port device (r-Port) was introduced percutaneously into the bladder through a 2.5-cm incision under cystoscopic guidance. After establishing pneumovesicum, the adenoma was enucleated in its entirety transvesically under laparoscopic visualization using standard and articulating laparoscopic instrumentation. The adenoma was extracted through the solitary skin and bladder incision after bivalving the prostate lobes within the bladder. Results: Single-port transvesical enucleation of the prostate was technically feasible in all 3 cases. The operative time was 6, 1.5, and 2.5 hours, and the blood loss was 900, 250, and 350 mL. In patient 1, who had previously undergone open suprapubic surgery, a bowel injury occurred during r-Port insertion; the injury was recognized and repaired intraoperatively without sequelae. The urethral Foley catheter was removed on day 4, and all patients were voiding spontaneously with a minimal postvoid residual volume and full continence. Conclusions: Transvesical single-port laparoscopic simple prostatectomy is technically feasible. Additional experience at our and other institutions is necessary to determine its role in the surgical management of large-volume symptomatic benign prostatic hyperplasia. © 2008 Elsevier Inc. All rights reserved.