Objective: To investigate the association between serum cholesterol concentration and cerebrovascular disease. Design: Retrospective study. Setting: Acute stroke unit of inner city general hospital. Subjects: 977 patients with acute stroke. Main outcome measures: Serum total cholesterol concentration, type of stroke investigated by computed tomography or magnetic resonance imaging, three month outcome (good (alive at home) or bad (dead or in care)), long term mortality. Results: After adjustment for known prognostic factors, higher serum cholesterol concentrations were associated with reduced long term mortality after stroke (relative hazard 0.91 (95% confidence interval 0.84 to 0.98) per mmol/l increase in cholesterol) independently of stroke type, vascular territory and extent, age, and hyperglycaemia. Three month outcome was also influenced independently by serum cholesterol (P=0.024). Conclusions: Our data suggest an association between poor stroke outcome and lower serum cholesterol concentration. Until a prospective controlled study has confirmed the benefits of lowering cholesterol concentration in elderly subjects, the application of cholesterol lowering guidelines cannot be justified as secondary prevention of acute stroke. Although the link between cholesterol and stroke is controversial, the balance of evidence suggests higher cholesterol is associated with an increased risk of atherothrombotic stroke but a reduced risk of intracerebral haemorrhage Trials of lipid lowering drugs have concentrated on middle aged patients with a relatively low incidence of stroke events We investigated the association between serum cholesterol and cerebrovascular disease in 977 patients hospitalised with acute stroke and found that higher serum total cholesterol concentrations were associated with a reduction in long term mortality after stroke This relation was independent of the type or extent of the stroke, vascular territory, age, and hyperglycaemia–all factors known to influence survival independently after stroke Until conclusive benefit is shown in elderly patients with cerebrovascular disease, the routine application of lipid lowering treatment after stroke cannot be justified