The aim of this study is to evaluate the outcomes of thulium laser vaporesection of prostates with volume exceeding 100 cm3. In the present prospective study, patients with infra-vesical urinary obstruction due to a prostate with volume exceeding 100 cm3 underwent endoscopic vaporesection using thulium laser. In this procedure, prostate chips were resected without morcellation. The technical aspects of surgery, admission time, post-operative catheter time and post-operative complications were analyzed. Flowmetry was performed combined with prostatic ultrasound in the follow-up. Between March 2010 and November 2018, 156 cases with benign prostatic hyperplasia (BPH; volume >100 cm3) were treated. The mean patient age was 67.8 years (48.4–86.6 years), and the mean prostatic volume was 137 cm3 (100–436 cm3). The mean length of hospitalization was 1.48 days (1–8 days), and the mean post-operative catheter time was 5.1 (1–17). Three cases (1.9%) required readmission due to hematuria. The mean follow-up time was 31.2 months (standard deviation = 27.7). Urethral stricture was observed in 14 cases (9%), with bulbar urethra being the most frequent finding. Urinary tract infection was observed in 11 cases (7.1%), and urinary incontinence was observed in 5 cases. The mean peak urinary flow at 12 and 24 months was 26.9 ± 12.5 and 23.9 ± 11.7 ml/s, respectively, and the mean urinary flow during the final follow-up at 41 months was 21.6 ml/s. Thulium laser vaporesection is a valid alternative to open prostatectomy, HoLEP and ThuLEP in patients with large BPH. Urinary flow remained elevated throughout the follow-up.