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Objectives: Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV., Methods: We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries., Results: A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)]., Conclusion: AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)