BACKGROUND: Peripheral nerve biopsy is a valuable final diagnostic tool, however histopathological results can be non-diagnostic. AIMS: We aim to identify quality improvement measures by evaluating the pre-biopsy assessment and diagnostic yield of specific histopathological diagnosis. METHODS: This was a retrospective study based on ten years of experience with peripheral nerve biopsies at a single centre. Clinical data was obtained regarding pre-biopsy history, examination, serum and CSF investigations, neurophysiology and peripheral nerve imaging. Based upon a histopathological outcome, patients were grouped into vasculitis, granulomatous and infiltrative ("diagnostic") group, or a comparison group of non-specific axonal neuropathy and normal ("non-specific/normal") group. RESULTS: From a cohort of 64 patients, 21 (32.8%) were included in the diagnostic group and 30 (46.9%) in the non-specific/normal group. Clinical parameters associated with the diagnostic group were shorter history (mean 10.2 months vs 38.1), stepwise progression (81% vs 20%), neuropathic pain (85.7% vs 56.7%), vasculitic rash (23.8% vs 0%), mononeuritis multiplex (57.1% vs 10%), asymmetry (90.5% vs 60%), raised WCC (47.6% vs 16.7%), myeloperoxidase antibody (19.1% vs 0%) and abnormal peripheral nerve imaging (33.3% vs 10%). CONCLUSIONS: Selection of patients undergoing nerve biopsy requires careful consideration of clinical parameters, including peripheral nerve imaging. Several quality improvement measures are proposed to improve yield of clinically actionable information from nerve biopsy. This article is protected by copyright. All rights reserved.