Purpose: To evaluate the efficacy and safety of GreenLight HPS™ laser photoselective vaporization of the prostate (PVP) for the treatment of benign prostatic hyperplasia (BPH) in patients with different prostate volumes. Patients and Methods: Between July 2006 and February 2011, 207 consecutive patients were identified from a prospectively maintained urologic database. Based on preoperative prostate volume measured by transrectal ultrasonography, patients were stratified into two groups: ≥80 cc (group 1, n=57) and <80 cc (group 2, n=150). Transurethral PVP was performed using a 120W GreenLight HPS side-firing laser system. American Urological Association Symptom Score (AUASS), quality-of-life (QoL) score, maximum flow rate (Qmax), and postvoid residual (PVR) volume were measured preoperatively and at 1 and 4 weeks and 3, 6, 12, 18, 24, and 36 months postoperatively. Results: Among the preoperative parameters evaluated, there were significant differences (P<0.05) in the incidence of preoperative urinary retention (1: 24.6%; 2: 7.3%), serum prostate-specific antigen level (1: 4.5±2.7; 2: 1.8±1.9 ng/mL), QoL (1: 4.2±1.1; 2: 4.7±0.9), and mean prostate volume (1: 118.1±37.9; 2: 48.5±15.5 cc), while AUASS, Qmax, and PVR were similar (P>0.05) between groups. Significant differences (P<0.05) in laser use (1: 22.8±13.3; 2: 10.4±6.4 minutes) and energy usage (1: 152.7±90.6; 2: 70.9±44.8 kJ) were also noted. Clinical outcomes (AUASS, QoL, Qmax, and PVR) showed immediate and stable improvement from baseline (P<0.05) within each group, but no significant differences between the two groups were observed during the follow-up period (P>0.05). The incidence of adverse events was low and similar in both cohorts. Conclusions: These results suggest that prostate volume has little effect on the efficacy and safety of GreenLight HPS laser PVP, and that this technique remains a viable surgical option for BPH, irrespective of preoperative prostate volume.