Open simple prostatectomy has been considered the treatment of choice for symptomatic benign prostatic hyperplasia (BPH) of large prostates because traditional endoscopic techniques have not proven either effective or feasible. We present our experience with holmium laser enucleation of the prostate (HoLEP) for glands >175 cc. An Institutional Review Board approved prospective database has been maintained since January 1999 for all HoLEP procedures. The database was reviewed retrospectively for patients who underwent HoLEP for BPH with a preoperative transrectal ultrasonography (TRUS) volume of >175 cc. From January 1999 to November 2008, we identified 57 patients with a mean pretreatment TRUS volume of 217.8 cc (range 175-391 cc). Preoperative retention was present in 30 patients. Preoperative mean prostate-specific antigen level was 14.6 ng/mL, mean American Urological Association (AUA) symptom index was 19.0, and mean peak flow (Qmax) was 8.2 mL/sec. Mean hospital stay was 26 hours, and postoperative catheterization was 18.5 hours (range 6-96 hrs). All patients were able to void after catheter removal. Mean enucleated tissue weight was 176.4 g (range 48-532.2 g). At 6-month follow-up, AUA symptom index was 6.5, mean PSA level was 0.78 ng/mL, and Qmax was 18.5. During the follow-up period, no patient needed catheterization or had persistent incontinence. Even in the large prostate gland, HoLEP provides a satisfactory outcome with low morbidity. HoLEP is the only endoscopic technique that allows for tissue removal comparable to that of open prostatectomy for such patients.