Meningitis following endoscopic trans-nasal surgery is a serious neurological complication. Risk factors for meningitis include post-operative cerebrospinal fluid (CSF) leak and redo-procedures. Pre-operative antiseptic wash is routinely used in neurosurgery however the impact and effectiveness of antiseptic wash in the nasal cavity is questionable due to the length of the surgical corridor and anatomical configuration of the nasal cavity. Our objective was to assess the hypothesis, that pre-operative antiseptic wash has no impact on the incidence of post-operative meningitis in endoscopic anterior skull base surgery. A prospective multi-centre database was interrogated to identify two cohorts of patients, separated into a no antiseptic wash group (NoPREP) and an antiseptic wash group (PREP). For each patient, clinical presentation, endocrine profile, MR imaging findings, operative details including intra-operative CSF leaks, post-operative complications and tumour pathology were identified. All patients diagnosed with post-operative meningitis were identified and case notes reviewed in detail. We found 453 consecutive patients that were separated into the PREP (n = 318) and NoPREP groups (n = 135). Both groups were well matched apart from a higher preponderance of meningiomas treated in the NoPREP group. Seven (1.5%) cases of post-operative meningitis were identified with no difference in meningitis incidence between the groups (PREP = 5 [1.6%]; NoPREP = 2 [1.5%]; p = 1). Post-operative CSF leak was identified as a significant risk factor for post-operative meningitis regardless of patient group (p < 0.001). We conclude that pre-operative antiseptic wash has no effect on the incidence of post-operative meningitis following endoscopic trans-nasal surgery. Post-operative CSF leak is the most significant risk factor in this regard.