OBJECTIVE: To compare the short-term oncological and HRQOL outcomes between open (ORP) and robotic-assisted (RARP) radical prostatectomy in the population-based Victorian Prostate Cancer Registry (PCR). PATIENTS AND METHODS: This is a prospective cohort of prostate cancer patients who had RP (1117 ORP and 885 RARP) between January 2009 and June 2012. The oncological outcomes of interest were: positive surgical margin (PSM) and biochemical recurrence (BCR) (defined as post-operative PSA >0.2ng/ml). The HRQOL outcomes were: sexual and urinary bother, assessed using the Expanded Prostate Cancer Index Composite (EPIC) at 1- and 2-year post-diagnosis. Student T-test or Mann-Whitney U-test were used for univariate comparison of continuous variables, and Pearson’s chi-squared test for categorical variables. Bonferonni correction was applied to account for multiple testing, with threshold for significance of P<0.003 for univariate analyses. The inverse probability treatment weighting (IPTW) approach was used to adjust for differences in baseline characteristics between ORP and RARP patients (including age, NCCN risk categories, hospitals, and year of RP) in all multivariate analyses. Logistic regressions were used to analyse for PSM, Cox regressions for BCR, and ordinal logistic regressions for HRQOL outcomes. All multivariate analyses also adjusted for surgeons' average annual caseload, and employed the robust standard errors for clustering by surgeon. RESULTS: ORP and RARP patients were followed for a median of 19 months and 17 months respectively. The proportion of patients with NCCN low risk prostate cancer was significantly higher among RARP patients (21% vs. 26%; P=0.002). The majority of RP was done in the private sector (77% ORP, and 85% RARP, P<0.001). A higher proportion of RARP patients were operated by surgeons with higher annual caseload (65% RARP and 53% ORP operated by surgeons with >20 case/ year (P<0.001). In the IPTW-adjusted multivariate analyses, RARP patients had lower risk of PSM (OR=0.56; 95%CI=0.38-0.81), and BCR (HR=0.73; 95%CI=0.55-0.99). In the sensitivity analyses (excluding public hospital patients), the lower PSM risk with RARP remains (OR=0.63; 95%CI=0.38-0.81), but the lower BCR risk with RARP was no longer statistically significant (HR=0.79; 95%CI=0.57-1.12). At 1 year follow-up, 61% ORP and 59% RARP patients reported moderate-big sexual bother (P=0.2), while 14% ORP and 11% RARP patients reported moderate-big urinary bother (P=0.08). The sexual and urinary bother at 2-year was similar between ORP and RARP. No statistically significant differences in the HRQOL outcomes between ORP and RARP were observed in multivariate analyses. CONCLUSION: We reported a large population-based comparative study on ORP and RARP with better short-term oncological outcomes favouring RARP, but no significant differences in HRQOL outcomes. The results have to be interpreted, taking into account significant surgeon heterogeneity, in a population-based study. This article is protected by copyright. All rights reserved.