Abstract Background Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are frequent and life-threatening complications of ischemic stroke. We evaluated rates of symptomatic DVT/PE, and of in-hospital and post-discharge thromboprophylaxis in patients with acute ischemic stroke (AIS). Methods In a retrospective US database analysis, data were extracted from the Premier Perspective™-i3 Pharma Informatics linked database for patients aged ≥18 years who were hospitalized for ischemic stroke from January 2005 to November 2007, and who had ≥6 months’ continuous plan enrollment prior to index hospitalization. Patients discharged to an acute-care facility or with atrial fibrillation were excluded. Prophylaxis was evaluated during index hospitalization and for 14 days’ post-discharge. DVT/PE rates were calculated during index hospitalization and up to 30 days post-discharge. Results A total of 1524 patients were included; 46.1% received pharmacological and/or mechanical prophylaxis in-hospital (28.3%, 11.4% and 12.3% received unfractionated heparin, enoxaparin and mechanical prophylaxis, respectively). 6.4% of patients received outpatient pharmacological prophylaxis; warfarin was most frequently prescribed (5.9%). Total mean ± standard deviation length of index hospitalization was 3.0 ± 2.5 days. Mean prophylaxis duration in all patients was 0.9 ± 1.5 days in-hospital and 1.7 ± 6.9 days post-discharge. Symptomatic DVT/PE occurred in 25 patients overall (1.64%), with an inpatient rate of 0.98% and an outpatient rate of 0.66%. Conclusions Approximately 1% of patients with AIS experienced symptomatic in-hospital and/or post-discharge DVT/PE. Although 46% received prophylaxis in-hospital, only 6% received prophylaxis in the outpatient setting. This highlights the need for sustained thromboprophylaxis prescribing across the continuum of care.