RESULTS• Of all 188 prostatectomy specimens, 49 (26.1%) had positive surgical margins (PSM); these were found posterolaterally in 15 (30.6%), apically in 13 (26.5%), basally in 10 (20.4%) and at multiple sites in 11 (22.4%) specimens.• Intraoperative peripheral FS were positive in 19 (10.7%) patients, including 6.2% at urethral stump, 3.3% at lateral pedicles and 1.1% at bladder neck.• In organ-confined disease, BCR-free survival was 93.3% (111/119) for patients with negative surgical margins (NSM) and 72% (18/25) for patients with PSM (inked specimen), but negative peripheral FS ( P < 0.001).• Five-and 10-year BCR-free survival for NSM was 94.9% and 92.8%, for PSM with negative peripheral FS it was 75.3% and 70.6%, and for PSM with positive peripheral FS it was 62.5% and 62.5%, respectively. CONCLUSIONS• Frozen section biopsies of peripheral resection margins during nerve-sparing radical prostatectomy are not reliable in predicting PSM.• Intraoperative achievement of a locally disease-free status, as monitored by negative circumferential intraoperative FS of peripheral margins, is not associated with a statistically significant BCR-free survival benefit compared with patients with negative surgical margins on the prostatectomy specimen.• Based on these findings, we do not recommend a routine of systematically taking intraoperative FS biopsies during nerve-sparing radical prostatectomy. KEYWORDSfrozen sections, prostate cancer, prostate neoplasms, prostate-specific antigen, retropubic prostatectomy What's known on the subject? and What does the study add? We hypothesized that taking intraoperative frozen section (FS) biopsies of the peripheral margins of resection during radical prostatectomy would allow an intraoperative systematic scan of resection margins. In the case of positive FS, extended resection could be performed with the aim of completely excising residual tumour, improving biochemical recurrence-free survival of patients with positive surgical margins at the inked specimen. To our knowledge, the prognostic value of achieving a negative resection status by systematically taking intraoperative FS of the peripheral margins of resection during radical prostatectomy has not been established to date.Study Type -Therapy (outcomes research) Level of Evidence 2b OBJECTIVE• To determine the value of systematic intraoperative peripheral frozen sections (FS) with or without extended resection during nerve-sparing radical prostatectomy for prediction of biochemical recurrence (BCR) compared with inked surgical margins. Between 1999 and 2003, in a prospective study, multiple peripheral FS (median 14; range 5-20) were taken from the urethral stump, circumferentially from the bladder neck, and from the lateral pedicles in 200 consecutive bilateral nerve-sparing radical prostatectomies for clinically localized prostate cancer by a single surgeon. PATIENTS AND METHODS •• Patients with stage pT3b or more and/or positive lymph nodes were excluded.• Of the 188 patients, 178 (94.7%) were followed over a median of 82 m...