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Introduction: Additional insight in the occurrence and number of positive surgical margins (PSM) and the potential consequences is needed, since earlier studies show divergent results. This study aims at investigating the effect of the presence and number of PSM on oncological outcomes. Methods: Retrospective population-based cohort study including 648 consecutive prostate cancer patients who underwent RP in the Southern Netherlands in 2006-2008. The effect of PSM on risk of treatment failure, defined by either biochemical recurrence or necessity of any additional therapy (Cox regression), was evaluated. Results: PSM were observed in 39%; 11% had multiple PSM. Treatment failure was observed in 26% of all patients. Multivariably, the presence (hazard ratio 2.5) and number of PSM (hazard ratios: single 2.3; multiple 3.1) were independently associated with higher treatment failure rates, unlike location of PSM. Conclusions: Treatment failure rates are high among patients with PSM, especially in those with multiple PSM. This needs to be taken into account when decisions are made on the applicability of the adjuvant and salvage therapy. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]