© Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Objective To compare cancer detection rates and concordance between magnetic resonance imaging and ultrasound (MRI-US) fusion-guided prostate biopsy cores obtained from axial and sagittal approaches. Patients and Methods Institutional records of MRI-US fusion-guided biopsy were reviewed. Detection rates for all cancers, Gleason ≥3 + 4 cancers, and Gleason ≥4 + 3 cancers were computed. Agreement between axial and sagittal cores for cancer detection, and frequency where one was upgraded the other was computed on a per-target and per-patient basis. Results In all, 893 encounters from 791 patients that underwent MRI-US fusion-guided biopsy in 2007-2013 were reviewed, yielding 4688 biopsy cores from 2344 targets for analysis. The mean age and PSA level at each encounter was 61.8 years and 9.7-ng/mL (median 6.45-ng/mL). Detection rates for all cancers, ≥3 + 4 cancers, and ≥4 + 3 cancers were 25.9%, 17.2%, and 8.1% for axial cores, and 26.1%, 17.6%, and 8.6% for sagittal cores. Per-target agreement was 88.6%, 93.0%, and 96.5%, respectively. On a per-target basis, the rates at which one core upgraded or detected a cancer missed on the other were 8.3% and 8.6% for axial and sagittal cores, respectively. Even with the inclusion of systematic biopsies, omission of axial or sagittal cores would have resulted in missed detection or under-characterisation of cancer in 4.7% or 5.2% of patients, respectively. Conclusion Cancer detection rates, Gleason scores, and core involvement from axial and sagittal cores are similar, but significant cancer may be missed if only one core is obtained for each target. Discordance between axial and sagittal cores is greatest in intermediate-risk scenarios, where obtaining multiple cores may improve tissue characterisation.