Objectives Aneurysm re-rupture is associated with significant morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). While antifibrinolytics reduce aneurysm re-rupture rates, they have been associated with hydrocephalus, delayed cerebral ischemia, and venous thrombosis. We performed a case-control study in patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study to evaluate the impact of short course (<48 h) ε-aminocaproic acid (EACA) on deep venous thrombosis (DVT) rates. Patients and methods A case-control study design was utilized to evaluate the effect of EACA on DVT formation. All cases and controls were obtained from the CARAS study, a prospective, blinded study assessing the association of polymorphisms in the renin angiotensin system and aSAH. Results One hundred and twenty-eight eligible patients were enrolled in CARAS. Overall, 48 (37.5%) patients were screened for DVT, 57 (44.5%) patients were treated with short course (<48 h) EACA, and 8 (6.3%) patients suffered a re-rupture (4 treated with EACA). Ten patients (7.8%) were diagnosed with DVT as evidenced by Doppler US and represent the cases. Twenty controls without evidence of a DVT matched for age, sex, race, tobacco history, Hunt-Hess score, Fisher grade, body mass index, and length of stay were identified from the remaining pool of 118 patients. EACA was found to significantly increase the risk of DVT formation in patients with aSAH (OR 8.49, CI 1.27-77.1). Conclusion Short course (<48 h) administration of EACA in patients with aneurysmal subarachnoid hemorrhage is associated with an 8.5 times greater risk of DVT formation.