Although dyslipidemia increases the risk for ischemic stroke, previous studies reported conflicting data regarding the association between lipid levels and stroke severity and outcome. To evaluate the predictive value of major lipids in patients with acute ischemic stroke. We prospectively studied 790 consecutive patients who were admitted with acute ischemic stroke (41.0 % males, age 79.4 ± 6.8 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Moderate/severe stroke was defined as NIHSS ≥5. The outcome was assessed with dependency rates at discharge (modified Rankin scale between 2 and 5) and with in-hospital mortality. Independent predictors of moderate/severe stroke were age (relative risk (RR) 1.05, 95 % confidence interval (CI) 1.02-1.08, p < 0.001), atrial fibrillation (RR 1.71, 95 % CI 1.19-2.47, p < 0.005), heart rate (RR 1.02, 95 % CI 1.01-1.04, p < 0.001), log-triglyceride (TG) levels (RR 0.24, 95 % CI 0.08-0.68, p < 0.01) and high-density lipoprotein cholesterol (HDL-C) levels (RR 0.97, 95 % CI 0.95-0.98, p < 0.001). Major lipids did not predict dependency at discharge. Independent predictors of in-hospital mortality were atrial fibrillation (RR 2.35, 95 % CI 1.09-5.04, p < 0.05), diastolic blood pressure (RR 1.05, 95 % CI 1.02-1.08, p < 0.001), log-TG levels (RR 0.09, 95 % CI 0.01-0.87, p < 0.05) and NIHSS at admission (RR 1.19, 95 % CI 1.14-1.24, p < 0.001). Low-density lipoprotein cholesterol levels were not associated with stroke severity or outcome. Lower TG and HDL-C levels are associated with more severe stroke. Lower TG levels also appear to predict in-hospital mortality in patients with acute ischemic stroke.