Aspirin is the standard treatment for acute ischemic stroke, although heparins are widely prescribed. We performed a systematic review of randomized controlled trials to compare the safety and efficacy of low molecular weight heparins (LMWH) with aspirin in acute ischemic stroke. Two completed randomized controlled trials involving 1,933 patients were identified; 1 trial only included patients with presumed cardioembolic stroke. As compared with aspirin, treatment with heparin was associated with a significant reduction in symptomatic venous thromboembolism (odds ratio [OR]--0.29, 95% confidence interval [CI]--0.12-0.66) and an increase in major extracranial hemorrhage (OR--2.57, 95% CI--1.01-6.52). Nonsignificant increases in end-of-treatment case fatality (OR--1.35, 95% CI--0.87-2.08) and symptomatic intracranial haemorrhage (OR--1.82, 95% CI--0.68-4.87) were seen; symptomatic intracranial haemorrhage was significantly raised (OR--4.26, 95% CI--1.04-17.4) with heparin in patients treated within 24 hours of stroke onset. Stroke recurrence (OR--1.24, 95% CI--0.79-1.94) and deterioration (OR--1.13, 95% CI--0.85-1.50) during treatment and end-of-trial death (OR--1.00, 95% CI--0.77-1.30) or dependency and case fatality (OR--1.03, 95% CI--0.85-1.25) did not differ between the 2 treatments. No benefit of LMWH over aspirin was seen in patients with presumed cardioembolic stroke. Low molecular weight heparin should not replace aspirin in the routine management of patients with ischemic stroke, including those with presumed cardioembolic stroke.