Background: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), the most frequently used lipid-lowering agents (LLAs) have neuroprotective effects in rodent models of ischemic stroke. The authors hypothesized that patients with ischemic stroke taking LLAs would have better outcomes than patients not taking LLAs. Methods: The Northern Manhattan Study is a population-based study designed to determine stroke incidence and prognosis in a multiethnic, urban population. Northern Manhattan residents age 40 years or older diagnosed with their first ischemic stroke were eligible. Patients or their proxies were interviewed regarding medications being taken at home before stroke onset. The NIH Stroke Scale was used to assess stroke severity, categorized as mild (≤5), moderate (6 to 13), or severe (≥14), and the Barthel Index at 6 months to assess functional outcome. Clinical worsening in hospital was recorded by trial neurologists. Odds ratios and 95%CIs for association of LLA use and stroke severity, mortality, and functional outcome were calculated using logistic regression. Results: Of 650 patients, 57 (8.8%) were taking LLAs. The majority (90.9%) of LLA users were taking a statin. Clinical worsening in hospital occurred less frequently among patients taking LLAs at stroke onset (6.3%vs 18.2%; p=0.04). Ninety day mortality was lower in those taking LLAs (1.8%vs 10.6%, p=0.03). The proportion of patients with severe stroke among those taking LLAs was not lower (10.7%vs 16.8%, p=0.39). Conclusion: Patients taking lipid-lowering agents (LLAs) at the time of an ischemic stroke may have lower poststroke mortality and a lower risk of worsening during hospitalization. Prospective studies are warranted to determine whether LLAs, and statins in particular, have neuroprotective properties or other beneficial effects in acute ischemic stroke. The most frequently used lipid-lowering agents (LLAs) have neuroprotective effects in rodent models of ischemic stroke. The authors hypothesized that patients with ischemic stroke taking LLAs would Methods: The Northern Manhattan Study is a population-based study designed to determine stroke incidence and prognosis in a multiethnic, urban population. Northern Manhattan residents age 40 years or older diagnosed with their first ischemic stroke were eligible. Patients or their proxies were interviewed regarding medications being taken at home before stroke onset. The NIH Stroke Scale was used to assess stroke severity, categorized as mild (≤5), moderate (6 to 13), or severe (≥14) , and the Barthel Index at 6 months to assess functional outcome. Clinical worsening in hospital was recorded by trial neurologists. Odds ratios and 95% CIs for association of L Results: Of 650 patients, 57 (8.8%) were taking LLAs. The majority (90.9%) of LLA users were taking a statin. Clinical worsening in hospital occurred less frequently among patients taking LLAs at stroke onset (6.3% vs 18.2%; p = 0.04). Ninety day mortality was lower in those taking LLAs (1.8% vs 10.6%, p = 0.03) Among those taking LLAs was not lower (10.7% vs 16.8%, p = 0.39). Conclusion: Patients taking lipid-lowering agents (LLAs) at the time of an ischemic stroke may have lower poststroke mortality and a lower risk of worsening during hospitalization Prospective studies are warranted to determine whether LLAs, and statins in particular, have neuroprotective properties or other beneficial effects in acute ischemic stroke.