Abstract Background Ongoing efforts are focused on minimizing or eliminating renal ischemia during robot-assisted partial nephrectomy (RPN). Although various techniques allowing the elimination of renal hilar clamping have been described, large multi-institutional studies assessing perioperative and functional outcomes of this approach are lacking. Objective To evaluate perioperative and functional outcomes of RPN without hilar clamping and to assess comparative effectiveness relative to clamped RPN. Design, setting, and participants A multi-institutional data analysis of prospectively collected records of 886 RPNs performed by high-volume surgeons across five academic institutions between 2007 and 2011 was carried out. A total of 66 patients who underwent RPN without hilar clamping were identified. After the exclusion of 17 patients, perioperative results of 49 patients were compared against propensity score matched clamped controls. Intervention RPN without hilar clamping. Outcome measurements and statistical analysis Descriptive statistics and propensity score matching. Results and limitations Patients undergoing off-clamp RPN had a mean tumor size of 2.5cm (standard deviation [SD]: ±2.1) and a mean RENAL nephrometry score of 5.3 (SD: ±1.5). The mean preoperative estimated glomerular filtration rate (eGFR) was 81 (SD: ±29). The mean estimated blood loss (EBL) was 210ml (SD: ±212), and the mean operative time was 155min (SD: ±46). No Clavien 3–5 complications were recorded. The mean postoperative change in eGFR was 3% at first follow-up (1–3 mo), and no patient required postoperative dialysis. The positive surgical margin rate was 3% (n=2), with no disease recurrence reported at a mean follow-up of 21 mo. In propensity score matched analyses, the off-clamp RPN patients had a significantly shorter mean operative time (156min compared with 185min, p<0.001), a higher EBL (228ml compared with 157ml, p=0.009), and a smaller decrease in eGFR (2% compared with −6%, p=0.008). The retrospective analysis was the main limitation of this study. Conclusions With appropriately selected patients and adequate surgeon experience, off-clamp RPN is safe and feasible. Off-clamp RPN was associated with higher EBL, shorter operative times, and smaller decrease in renal function.