Background and aims In inflammatory bowel disease (IBD), the impact of established cardiovascular risk factors and disease-related factors on the risk of acute arterial events is still unclear. We aimed to identify risk factors of acute arterial events in patients with IBD. Methods All consecutive patients followed at Saint-Antoine Hospital between 1996 and 2015 with subsequent occurrence of acute arterial events (acute coronary syndrome or ischemic stroke) were identified. Traditional cardiovascular risk factors, treatment exposure, systemic inflammation (mean serum CRP level greater than or equal to 5 mg/L) and IBD clinical activity were assessed. A nested case-control study was performed including cases and controls without arterial ischemic event, matched on age, gender, and disease extent. Results A total of 30 patients (median age at acute vascular event occurrence: 42 years (interquartile range: 25–59)) developed acute coronary syndrome (n = 22) or ischemic stroke (n = 8). In univariate analysis, clinical disease activity and the persistence of systemic inflammation, diabetes, dyslipidemia and hypertension were significantly associated with an increased risk of acute arterial events. Neither protective nor aggravating effects associated with treatment exposure were identified. In multivariate analysis, the presence of diabetes (Odds ratio (OR): 14.5, 95% confidence interval (CI): 1.1–184.7) and clinical disease activity (OR: 10.4, 95% CI: 2.1–49.9) remained significantly associated with the risk of acute arterial event. Conclusion Disease activity may have an independent impact on the risk of acute arterial events in patients with IBD. These findings may highlight new potential benefits of optimizing anti-inflammatory treatment in patients with persisting clinical activity.