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Objective: To assess the prognostic significance of positive surgical margins (PSMs) after minimally invasive radical prostatectomy (MIRP) in interaction with other established prognosis factors., Patients and Methods: We retrospectively analysed data prospectively collected between 1998 and 2010 for 4628 consecutive patients who underwent MIRP for clinically localized prostate cancer. The impact of PSM on biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) >0.2 ng/mL, was evaluated using multivariable Cox proportional hazards regression. Estimates of BCR-free survival were generated using the Kaplan-Meier method and compared among groups using the log-rank test., Results: The median follow-up was 55 months. On multivariable analysis, PSM was an independent prognostic factor for BCR (adjusted hazard ratio: 2.14 for PSMs vs negative surgical margins (NSMs); 95% confidence interval [CI]: 1.86-2.45; P < 0.001). Other independent predictors for BCR were preoperative PSA, date of surgery, pT stage, Gleason score and lymph node involvement (all P < 0.001). The 5-year BCR-free probability was 80.6% (95% CI: 79-82.2) for NSMs vs 51% (95% CI: 47-55) for PSMs (log-rank P < 0.001). Patients with pT2 and pT3a PSMs had a similar prognosis to those with pT3a and pT3b NSMs, respectively (log-rank P ≥ 0.05)., Conclusion: A PSM after MIRP is associated with 2.14-fold increased risk of BCR. In patients with pT2 and pT3a disease, a PSM could be considered a pathological upstaging., (© 2013 The Authors. BJU International © 2013 BJU International.)