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Purpose: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis., Methods: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons., Results: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM., Conclusion: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated., (© 2024. Crown.)