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To assess cancer-detection rates in repeat 12-core biopsy protocols, as extended multicore prostate biopsy protocols have become standard when investigating men with a raised prostate-specific antigen (PSA) level, but repeat prostate biopsy protocols are still developing.During a 4.5-year period, 241 of 590 patients with persistently high age-specific PSA levels of 2.6–10 ng/mL and an initial benign biopsy were invited for repeat transrectal ultrasonography-guided 12-core prostatic biopsy. The protocol for repeat biopsy was identical to the first biopsy, and included a periprostatic nerve block. The first six biopsies were obtained from the periphery of the gland directed more laterally at the base, mid-zone and apices. The remainder were parasagittal sextant biopsies. Pathological findings were analysed on an individual core basis.The mean age of the 241 men was 63.4 years; cancer was diagnosed in 40 (16.6%) on repeat biopsy. Men with cancer were older and had a higher median PSA level. The median Gleason score was 6, with a median of two cores positive for cancer. Maximum cancer detection rates were from peripheral apices (37.5%), basal biopsies had the lowest detection rates (23.8% and 16.3%), and parasagittal biopsies missed 35% of detected cancers. Patients with cancer also had significantly lower prostate volumes and higher PSA densities (both P < 0.001).A low cancer yield from both peripheral basal and parasagittal basal specimens on repeat biopsy indicates adequate sampling at initial biopsy. The maximum cancer yield in the peripheral mid-zones and apical zones suggests the necessity for concentrated sampling of these zones in repeat biopsy protocols.