ABSTRACT: Background: Radical prostatectomy can be challenging in patients with a very large prostate. The extraperitoneal (EP) approach to a robot-assisted radical prostatectomy (RARP) is often considered more difficult than the transperitoneal approach due to the limited working space. The aim of the study is to evaluate if EP-RARP overcomes the obstacles posed by very large prostates. Methods: In this institutional review board-approved study, we queried our prospectively collected database (CAISIS) of patients who underwent EP-RARP. 1663 patients underwent EP-RARP for localized prostate cancer by a single surgeon (Jul. 2003–Dec. 2013). 55 patients with prostate pathology specimen weight >100g (group 1) were matched to an equally-sized cohort with prostate weight of <100 g (group 2). A propensity-score match using multivariate analysis was performed incorporating 10 co-variates. Data on standard pre, peri, and postoperative variables was analyzed, as well as complications classified according to the modified Clavien-Dindo classification were noted. Results: The mean PSA (9.1 ± 5.4 vs. 6.9 ± 5, p=0.03) was higher in group 1. All other patient and disease variables [Age (65.2 ± 5.6 vs. 63.3 ± 6, p=0.08), BMI (28.8 ± 3.4 vs. 29.3 ± 5, p=0.57), ASA 1/2/3 (7.2/72.7/20 vs. 10.9/69/20, p=0.8), clinical T-stage 1/2 (89/11 vs. 89/11, p=0.78), and biopsy Gleason score sum 7 (71/29 vs. 71/29, p=1) were similar in group 1 and 2 respectively. The mean prostate weight in group 1 was 120 g, while it was 58.6 g in group 2 (p<0.0001). There was no difference in the ability to perform partial or full nerve-sparing (70 vs 78 %, p=0.19) or pelvic lymphadenectomy (34.5 vs. 38.1 %, p=0.69). Post-operative pathological parameters such as Gleason score sum 7 (70.5/29.5 vs. 56.3/43.7, p=0.13), T-stage 2/3a/3b (89/7.2/1.8 vs. 87.2/10.9/1.8, p= 0.86) and positive surgical margin rates (7.2 vs. 9 %, p=1) were similar. Higher mean OR time (205.8 ± 48.6 vs 180.2 ± 43.4 mins, p=0.004) and estimated blood loss (318.4 ± 172.8 and 200.3 ± 143.5ccs, p=0.0002) were noted in group 1 compared to group 2 respectively. There were no differences in transfusion rates (1 patient transfused in group 2), rates of patients discharged on day 1 (89 vs. 94%, p=0.27), or the complications [Clavien 1–2/3–4 (11/2 vs 8/0, p=0.41)] between the two groups. Conclusions: Apart from increased operative times and blood loss, no differences in peri and postoperative parameters, and complications were found between patients with prostates > than 100 g compared to those with < 100 g undergoing EP-RARP.