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Active surveillance is a first line treatment option for patients with low risk prostate cancer but standardized regimens are lacking, including uniform protocols for surveillance prostate biopsy. We compared the outcomes of 2 active surveillance regimens that differ in whether a scheduled biopsy was performed in the absence of clinical progression.We retrospectively reviewed the records of 313 consecutive patients with prostate cancer at a NCCN® (National Comprehensive Cancer Network®) institution who were assigned prospectively to 1 of 2 active surveillance biopsy regimens. A total of 149 patients underwent biopsy only for clinical concern (for-cause only) while 164 underwent for-cause biopsy plus scheduled annual or biannual biopsy. Times to biopsy, clinical progression, pathological reclassification and treatment were compared using Kaplan-Meier methodology.The for-cause only and scheduled plus for-cause biopsy groups were similar in NCCN risk category at active surveillance initiation. Median followup was 48 and 38 months, respectively. No significant difference was observed in prostate specific antigen dynamics or clinical progression rates. However, patients in the scheduled plus for-cause group underwent significantly more frequent biopsies (p <0.001) and experienced more biopsy related complications (p = 0.04), pathological reclassification (p = 0.02) and treatment conversion (p = 0.001). Adverse prostatectomy pathology (pT3 or greater and/or Gleason primary pattern 4) and early metastasis events were rare in both groups.Omitting a scheduled biopsy during active surveillance is associated with a decreased biopsy burden and treatment conversion. Although no increase in adverse pathology or early metastasis was observed in this study, longer followup in larger cohorts is necessary to determine the impact of scheduled biopsy omission on these adverse outcomes.