Purpose: Positive surgical margins (PSM) during robot-assisted radical prostatectomy (RARP) negatively influence patients' prognosis. The aim of our study was to identify risk factors for PSM in patients with organ-confined prostate cancer (PCa). Methods: A clinical database of all patients that underwent a RARP at our institution was used. Uni- and multivariable logistic regression analyses were conducted on the PSM rates for all patients with organ-confined PCa. Results: Altogether, 1,600 patients were identified, including 1,085 organ-confined PCa with a PSM rate of 7.8%. On multivariable analysis, bilateral nerve-sparing (OR 3.025, 95% CI 1.587-5.765), surgeon volume <200 cases (OR 1.881, 95% CI 1.120-3.159) and a preoperative PSA >10 ng/ml (OR 3.674, 95% CI 1.379-9.796) remained independent prognostic factors. In a subgroup of patients undergoing a nerve-sparing RARP, the quality of the prostate biopsy (OR 2.398, 95% CI 1.325-4.341) was the sole independent risk factor for a PSM. Conclusion: An elevated preoperative PSA, surgical experience and a nerve-sparing procedure are all significantly associated with a higher risk for a PSM after RARP. For those undergoing a nerve sparing RARP, an accurate preoperative biopsy with detailed information on the location of positive cores is essential to prevent PSMs.