Background: Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the surgical trauma associated with conventional laparoscopy. Partial nephrectomy (PN) represents a challenging indication for LESS. Objective: To report a large multi-institutional series of LESS-PN and to analyze the predictors of outcomes after LESS-PN. Design, setting, and participants: Consecutive cases of LESS-PN done between November 2007 and March 2012 at 11 participating institutions were included in this retrospective analysis. Intervention: Each group performed LESS-PN according to its own protocols, entry criteria, and techniques. Outcome measurements and statistical analysis: Demographic data, main perioperative outcome parameters, and perioperative complications were gathered and analyzed. A multivariable analysis was used to assess the factors predicting a short (≤20 min) warm ischemia time (WIT), the occurrence of postoperative complication of any grade, and a favorable outcome, arbitrarily defined as a combination of the following events: short WIT plus no perioperative complications plus negative surgical margins plus no conversion to open surgery or standard laparoscopy. Results and limitations: A total of 190 cases were included in this analysis. Mean renal tumor size was 2.6, and PADUA score 7.2. Median operative time was 170 min, with median estimated blood loss (EBL) of 150 ml. A clampless technique was adopted in 70 cases (36.8%), and the median WIT was 16.5 min. PADUA score independently predicted length of WIT (low vs high score: odds ratio [OR]: 5.11 [95% confidence interval (CI), 1.50-17.41]; p = 0.009; intermediate vs high score: OR: 5.13 [95% CI, 1.56-16.88]; p = 0.007). The overall postoperative complication rate was 14.7%. The adoption of a robotic LESS technique versus conventional LESS (OR: 20.92 [95% CI, 2.66-164.64]; p = 0.003) and the occurrence of lower (≤250 ml) EBL (OR: 3.60 [95% CI, 1.35-9.56]; p = 0.010) were found to be independent predictors of no postoperative complications of any grade. A favorable outcome was obtained in 83 cases (43.68%). On multivariate analysis, the only predictive factor of a favorable outcome was the PADUA score (low vs high score: OR: 4.99 [95% CI, 1.98-12.59]; p < 0.001). Limitations of the study were the retrospective design and different selection criteria for the participating centers. Conclusions: LESS-PN can be safely and effectively performed by experienced hands, given a high likelihood of a single additional port. Anatomic tumor characteristics as determined by the PADUA score are independent predictors of a favorable surgical outcome. Thus patients presenting tumors with low PADUA scores represent the best candidates for LESS-PN. The application of a robotic platform is likely to reduce the overall risk of postoperative complications. © 2013 European Association of Urology.