Between September and December 2017, 82 men with moderate-to-severe lower urinary tract symptoms due to benign prostatic hyperplasia LUTS/BPH and prostate volume of 80-150 cc underwent Aquablation in a prospective multicenter clinical trial in the United States. Baseline patient and clinical demographics and standardized postoperative parameters were collected and tabulated in a central independently monitored database. Adverse events through 3 months were adjudicated by an independent clinical events committee. Mean pre-treatment prostate volume was 108 ± 21.1 cc. Mean operative time was 38.2 ± 14.4 min and mean Aquablation resection time was 7.7 ± 3.3 min. Additional electrocautery for hemostasis was not needed in any patient following Aquablation. The average length of stay following the procedure was 1.6 ± 1.0 days. Mean pre- and 3 months post-treatment IPSS scores were 23.7 ± 6.4 and 7.1 ± 5.1, -16.6, p < 0.01. Mean pre- and 3 months post-treatment Qmax were 9.2 ± 3.3 ml/s and 19.5 ± 13 ml/s, + 10.8 ml/s, p < 0.01. Mean pre- and 3 months post-treatment post-void residuals were 120.6 ± 119.1 cc and 50.6 ± 61.6 cc, -72.0 cc, p < 0.01. The observed Clavien-Dindo grade 2 or higher event rate at 3 months was 34.1%. Aquablation is a safe and effective treatment option for men with large prostates (80-150 cc) suffering from LUTS/BPH.